Methods for treating Crohn's disease and ulcerative colitis

Abstract

Methods for treating Crohn's disease using JAK1 inhibitors are provided, in particular methods for inducing clinical remission and / or endoscopic improvement of Crohn's disease. In certain embodiments, a patient is administered an induction dose of a JAK1 inhibitor to induce clinical remission and / or endoscopic improvement of Crohn's disease, followed by at least one maintenance dose of a JAK1 inhibitor. In other embodiments, the present disclosure is directed to methods for treating ulcerative colitis using a JAK1 inhibitor.

Description

[Technical Field]

[0001] This application claims priority to U.S. Provisional Application No. 62 / 469,337, filed March 9, 2017, U.S. Provisional Application No. 62 / 470,565, filed March 13, 2017, U.S. Provisional Application No. 62 / 483,289, filed April 7, 2017, and U.S. Provisional Application No. 62 / 593,629, filed December 1, 2017, each of which is incorporated by reference in its entirety.

[0002] The present disclosure is directed to methods for treating inflammatory bowel diseases such as Crohn's disease and ulcerative colitis using a JAK1 inhibitor, particularly methods for inducing clinical remission and endoscopic improvement in Crohn's disease or clinical remission and endoscopic improvement in ulcerative colitis. In certain embodiments, a patient is administered an induction dose of a JAK1 inhibitor to induce clinical remission and / or endoscopic improvement in Crohn's disease or clinical remission in ulcerative colitis, followed by at least one maintenance dose of a JAK1 inhibitor. [Background technology]

[0003] Inflammatory bowel disease (IBD) involves chronic inflammation of a patient's digestive tract. IBD includes both Crohn's disease and ulcerative colitis. The exact cause of IBD is unknown. IBD can be idiopathic.

[0004] Crohn's disease (CD) encompasses a variety of clinical and pathological processes manifested by focal, asymmetric, transmural, and occasionally granulomatous inflammation that can affect any segment of the gastrointestinal tract (Lichtenstein GR, Hanauer SB, Sandborn WJ; Practice Parameters Committee of the American College of Gastroenterology, Management of Crohn's disease in adults, Am J Gastroenterol. 2009;104(2):465-83). The disease can affect people of any age, with onset most common in those in their 20s and 30s. Women are slightly more susceptible than men, and the risk of developing the disease is higher in some ethnic groups (Loftus EV Jr., "Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences," Gastroenterology, 2004;126(6):1504-17; Probert CS, Jayanthi V, Rampton DS, et al., "Epidemiology of inflammatory bowel disease in different ethnic and religious groups: limitations and aesthetic clues," Int. J Colorectal Dis., 1996;11(1):25-28). In North America, the incidence of CD is estimated to be 3.1 to 14.6 cases per 100,000 people. The prevalence ranges from 26 to 99 cases per 100,000 people.In Europe, CD has an incidence of 0.7 to 9.8 cases per 100,000 people and a prevalence of 8.3 to 214 cases per 100,000 people (Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology. 2004;126(6):1504-17).

[0005] CD is characterized by significant morbidity, including abdominal pain, diarrhea, weight loss / malnutrition, fatigue, and a progressive nature leading to complications such as fistulas, strictures, and abscesses. In a population-based study from southeastern Norway, a substantial number of patients presented with a stricturing or penetrating phenotype 10 years after diagnosis (Solberg IC, Vatn MH, Hoie O, et al.; IBSEN Study Group. Clinical course in Crohn's disease: results of a Norwegian population-based ten-year follow-up study. Clin Gastroenterol Heptaol. 2007;5(12):1430-8). Furthermore, approximately 80% of patients diagnosed with CD will require at least one surgery for their disease at some point (Munkholm P, Langholz E, Davidsen M et al. Intestinal cancer risk and mortality in patients with Crohn's disease. Gastroenterology. 1993:105(6):1716-23).

[0006] Ulcerative colitis (UC) is one of the two major forms of idiopathic inflammatory bowel disease (IBD). UC is thought to be caused by an exaggerated and uncontrolled local immune response to environmental factors in genetically susceptible individuals (Hanauer SB. Update on the etiology, pathogenesis, and diagnosis of ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol. 2004;1(1):26-31). UC is a chronic, relapsing inflammatory disease of the large intestine characterized by inflammation and ulceration, primarily of the mucosa and occasionally of the submucosal intestinal layer. The highest annual incidence of UC is 24.3 per 100,000 people per year in Europe, 6.3 per 100,000 people per year in Asia and the Middle East, and 19.2 per 100,000 people per year in North America, with a prevalence of 505 cases per 100,000 people in Europe and 249 cases per 100,000 people in North America. (Molodecky NA, Soon IS, Rabi DM, et al., Increasing incidence and prevalence of inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012:142(1):46-54). Based on a systematic review, the incidence and prevalence of inflammatory bowel disease increase over time. (Gastroenterology. 2012;142(1):46-54. e42; quiz e30). The burden of UC on the healthcare system is significant, resulting in nearly 500,000 physician visits and over 46,000 hospitalizations annually in the United States (US) alone (Sandler RS, Everhart JE, Donowitz M, et al., Gastroenterology, 2002;122(5):1500-11).

[0007] The characteristic clinical symptoms of UC include bloody diarrhea accompanied by urgency and tenesmus. Its clinical course is characterized by exacerbations and remissions. The diagnosis of UC is suspected on clinical grounds and supported by diagnostic testing and the exclusion of infectious causes. (Dignass A, Eliakim R, Magro F, et al., Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 1: definitions and diagnosis. J Crohn's Colitis. 2012;6(10):965-90).

[0008] The most severe intestinal manifestations of UC are toxic megacolon and perforation. Extraintestinal complications include arthritis (peripheral or axial involvement), dermatological conditions (erythema nodosum, aphthous stomatitis, and pyoderma gangrenosum), eye inflammation (uveitis), and liver dysfunction (primary sclerosing cholangitis). Patients with UC are at increased risk for colon cancer, and this risk increases with the duration of disease and the extent of colon affected by the disease. (Rutter M, Saunders B, Wilkinson K, et al., Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology, 2004;126(2):451-9).

[0009] The goal of medical treatment for UC is to control inflammation and reduce symptoms. Available pharmaceutical treatments are limited, do not completely attenuate the inflammatory process, and may have significant adverse effects. Treatments for mild to moderately active UC include 5-aminosalicylic acid derivatives and immunosuppressants.

[0010] Corticosteroids are used in patients with more severe UC symptoms but are not useful for long-term treatment. (Truelove SC, Witts LJ. Cortisone and corticotrophin in ulcerative colitis. Br Med J. 1959;1(5119):387-94). The frequency and severity of corticosteroid toxicity are significant, including infections, emotional and psychiatric disorders, skin lesions, and metabolic bone disease. Corticosteroids are not effective in maintaining remission, and the American Gastroenterological Association's UC practice guidelines do not recommend long-term steroid treatment. (Kornbluth A, Sachar DB; Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults: American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010;105(3):501-23; quiz 524). Patients with moderate to severe symptoms may derive some benefit from immunosuppressants (azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX]), but the use of these agents is limited as induction treatment due to their slow onset of action (3–6 months) and as maintenance treatment due to adverse events (AEs), including myelosuppression, infection, hepatotoxicity, pancreatitis, and malignancy.(Kornbluth A, Sachar DB, disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study.Lancet.2009;374(9701):1617-25). Despite these treatments, approximately 15% of patients with ulcerative colitis experience a severe clinical course, and 30% of these patients require colon / rectum removal to eliminate the source of the inflammatory process, with significant morbidity (Aratari A, Papi C, Clemente V, et al., Colectomy rate in acute severe ulcerative colitis in the infliximab era. Dig Liver Dis. 2008;40(10):821-826; Turner D, Walsh CM, Steinhart AH, et al., Response to corticosteroids in severe ulcerative colitis: a systematic review of the literature and a meta-regression. Clin Gastroenterol Hepatol. 2007;5(1):103-10).

[0011] Biologic agents targeting specific immunological pathways are being evaluated for therapeutic efficacy in treating patients with UC. Anti-tumor necrosis factor (TNF) agents were the first biologics used for IBD. Infliximab, adalimumab, and golimumab have been successfully used for the treatment of UC. Recently, the anti-adhesion therapeutic agent vedolizumab was approved for the treatment of UC by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), and clinical development is underway in Japan.

[0012] Anti-TNF therapy is an effective treatment for patients who are steroid-resistant or steroid-dependent, have had an inadequate response to thiopurines, or are intolerant to these medications. Potential risks of using anti-TNF therapy include infusion or injection site reactions, serious infections, lymphoma, heart failure, lupus-like syndromes, and demyelinating conditions (Sandborn WJ. State-of-the-art: immunosuppression and biologic therapy. Dig Dis. 2010;28(3):536-42). Although beneficial results have been achieved with available biologic agents, only 17% to 45% of patients who take them achieve clinical remission. (Rutgeerts P, Sandborn W, Feagan B, et al., Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005, 353(23):2462-76; Sandborn WJ, van Assche G, Reinisch W, et al., Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis.Gastroenterology, 2012, 142(2):257~65;Feagan B, Greenberg G, Wild G, et al., Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin, N.Engl.J.Med.2005, 352(24):2499~507;Sandborn W, Feagan B, Marano C, et al., Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis, Gastroenterology, 2014, 146(1): pp. 85-95; quiz e14-5).Thus, there remains a clear medical need for additional treatment options for UC for patients who have an inadequate response or intolerance to conventional and biologic therapies.

[0013] Given that there is currently no known medical or surgical cure for CD, treatment strategies aim to reduce symptoms, improve quality of life, reduce endoscopic evidence of inflammation, and minimize short- and long-term toxicity and complications (Lichtenstein GR, Hanauer SB, Sandborn WJ; Practice Parameters Committee of the American College of Gastroenterology, Management of Crohn's disease in adults, Am J Gastroenterol. 2009, 104(2):465-83). Currently, patients with moderate to severe disease are usually treated with conventional pharmacological interventions, including corticosteroids and immunosuppressants such as azathioprine, 6-mercaptopurine, or methotrexate (MTX). (Lichtenstein GR, Hanauer SB, Sandborn WJ, Practice Parameters Committee of the American College of Gastroenterology, Management of Crohn's disease in adults, Am J Gastroenterol, 2009, 104(2):465-83; Dignass A, Van Assche G, Lindsay JO, et al., European Crohn's and Colitis Oganisation (ECCO), The second European evidence-based consensus on the diagnosis and management of Crohn's disease: current management, J Crohn's Colitis, 2010, 4(1):28-62; Erratum in: J Crohn's Colitis, 2010, 4(3):353).

[0014] The potential risks of long-term corticosteroid use are well known. Adverse events (AEs) associated with short-term corticosteroid use include acne, moon face, edema, striae, glucose intolerance, and sleep / mood disturbances, whereas potential AEs observed with longer-term use (usually 12 weeks or more, but occasionally shorter) include posterior subcapsular cataracts, osteoporosis, femoral head necrosis, myopathy, and susceptibility to infection (Irving PM, Geary RB, Sparrow MP, et al., Review article: appropriate use of corticosteroids in Crohn's disease, Aliment Pharmacol Ther., 2007; 26(3):313-29; Rutgeerts PJ, Review article: the limitations of corticosteroid therapy in Crohn's disease, Aliment Pharmacol Ther., 2001; 15(10):1515-25). Safety risks associated with azathioprine and 6-mercaptopurine include pancreatitis, bone marrow suppression, infectious complications, and malignant neoplasms (Sandborn, WJ, State-of-the-art: immunosuppression and biologic therapy, Dig Dis., 2010, 28(3):536-42). MTX can be associated with nausea, bone marrow suppression, and liver and lung toxicity (Siegel et al., Review article: Practical Management of Inflammatory Bowel Disease Patients Taking Immunosuppressants, Aliment Pharmacol Ther., 2005, 22:1-16).Patients who do not respond to conventional therapy are treated with anti-TNF-α therapy (i.e., biologics) (Lichtenstein GR, Hanauer SB, Sandborn WJ, Practice Parameters Committee of the American College of Gastroenterology, Management of Crohn's disease in adults, Am J Gastroenterol. 2009;104(2):465-83; Dignass A, Van Assche G, Lindsay JO, et al., European Crohn's and Colitis Oganisation (ECCO), The second European evidence-based consensus on the diagnosis and management of Crohn's disease: current management, J Crohn's Colitis 2010;4(1):28-62; Erratum in: J. Crohn's Colitis 2010;4(3):353). Potential risks of using biologics include infusion or injection site reactions, serious infections, lymphoma and other malignancies, heart failure, cytopenias, lupus-like syndromes, and demyelinating conditions (Sandborn WJ, State-of-the-art: immunosuppression and biologic therapy, Dig. Dis., 2010, 28(3):536-42).

[0015] Despite the beneficial results achieved with available anti-TNF-α agents, approximately 40% of patients who first receive them do not have a clinically meaningful response (primary non-responders) (Targan SR, Hanauer SB, van Deventer SJ, et al., A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease, N. Engl. J. Med., 1997, 337(15):1029-35; Hanauer SB, Feagan BG, Lichtenstein GR, et al., ACCENT I Study Group, Maintenance infliximab for Crohn's disease: the ACCENT I randomized trial, Lancet, 2002, 359(9317):1541-9; Hanauer SB, Sandborn WJ, Rutgeerts P, et al., Human anti-tumor necrosis factor monoclonal antibody(adalimumab) in Crohn's disease: the CLASSIC-I trial, Gastroenterology, 2007, 132(1):52-65; Colombel JF, Sandborn WJ, Rutgeerts P, et al., Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial, Gastroenterology, 2007, 132(1):52-65; Sandborn WJ, Feagan BG, Stoinov S et al., PRECISE I Study Investigators, Certolizumab pegol for the treatment of Crohn's disease, N.Engl.J.Med., 2007, 357(3):228-38).Of patients who initially respond and continue on long-term maintenance treatment, approximately 38% become non-responders after 6 months (Schribeinger S, Khaliq-Kareemi M, Lawrance IC, et al., PRECISE 2 Study Investigators, Maintenance therapy with certolizumab pegol for Crohn's disease, N. Engl. J. Med., 2007, 357(3):239-50; Erratum in: N. Engl. J. Med., 2007, 357(13):1357), and approximately 50% lose response and become non-responders at 1 year (secondary non-responders) (Hanauer SB, Feagan BG, Lichtenstein GR, et al., ACCENT I Study Group, Maintenance infliximab for Crohn's disease: the ACCENT I randomized trial, Lancet, 2002, 359(9317):1541-9; Colombel JF, Sandborn WJ, Rutgeerts P, et al., Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial, Gastroenterology, 2007, 132(1):52-65).Patients who initially respond to a first anti-TNF agent but later lose response tend to have reduced response and remission rates to a second anti-TNF agent (Colombel JF, Sandborn WJ, Rutgeerts P, et al., Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial, Gastroenterology, 2007, 132(1):52-65; Sandborn et al., "Natalizumab induction and maintenance therapy for Crohn's disease," N. Engl. J. Med., 2005, 353(18):1912-25).

[0016] A new class of biologics is being studied in patients previously treated with anti-TNF agents. Natalizumab, a humanized monoclonal antibody against α4β1 and α4β7 integrins, has shown promise in treating patients previously exposed to anti-TNF-α therapy, with more than half of patients responding to induction regimens (Sandborn et al., "Natalizumab induction and maintenance therapy for Crohn's disease," N. Engl. J. Med., 2005, 353(18):1912-25). However, since its approval in 2008, the use of natalizumab has been severely restricted due to the serious risk of progressive multifocal leukoencephalopathy (PML) resulting from activation of latent JC virus (Van Assche G, Van Ranst M, Sciot R, et al., "Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn's disease," N. Engl. J. Med., 2005, 353(4):362-368). Vedolizumab is specific for the α4β7 integrin, which does not affect lymphocyte trafficking to the brain. Therefore, it is assumed that there is no risk of PML associated with natalizumab. However, many unmet needs remain, such as improvement of extraintestinal symptoms, in patients who have failed anti-TNF treatment (Rubin et al., Inflammatory Bowel Diseases, 2016, 22 Suppl. 1:S42-S43). In an induction study with vedolizumab, the primary endpoint of clinical remission in patients who had previously failed anti-TNF treatment was only 3% different from placebo, which was neither statistically significant nor clinically meaningful (Sands et al., "Effects of Vedolizumab Induction Therapy for Patients With Crohn's Disease in Whom Tumor Necrosis Factor Antagonist Treatment Failed," Gastroenterology, 2014, 147:618-627).Ustekinumab, a human monoclonal antibody that selectively targets IL-12 and IL-23, is effective in both patients who have responded to and those who have not previously responded to anti-TNFα therapy. However, the efficacy of ustekinumab is similar to that of anti-TNF agents, and therefore its drawbacks are similar (Ther. Adv. Gastroenterology, 2016, Vol. 9(1), pp. 26-36). [Prior art documents] [Non-patent literature]

[0017] [Non-Patent Document 1] Lichtenstein GR, Hanauer SB, Sandborn WJ;Practice Parameters Committee of American College of Gastroenterology, Management of Crohn's disease in adults, Am J Gastroenterol.2009;104(2):465-83. [Non-patent document 2] Loftus EV Jr., "Clinical epidemiology of inflammatory bowel disease:incidence,prevalence,and environmental influences", Gastroenterology, 2004;126(6):1504-17 [Non-patent document 3] Probert CS, Jayanthi V, Rampton DS et al., "Epidemiology of inflammatory bowel disease in different ethnic and religious groups: limitations and aetiological clues," Int.J Colorectal Dis., 1996;11(1):25-28. [Non-patent document 4] Solberg IC, Vatn MH, Hoie O, et al.;IBSEN Study Group.Clinical course in Crohn's disease:results of a Norwegian population-based ten-year follow-up study.Clin Gastroenterol Heptaol.2007;5(12):1430~8 [Non-Patent Document 5] Munkholm P, Langholz E, Davidsen M, et al. Intestinal cancer risk and mortality in patients with Crohn's disease. Gastroenterology. 1993:105(6):1716-23 [Non-patent document 6] Hanauer SB.Update on the etiology, pathogenesis and diagnosis of ulcerative colitis.Nat Clin Pract Gastroenterol Hepatol.2004;1(1):pp.26~31 [Non-Patent Document 7] Molodecky NA, Soon IS, Rabi DM, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012:142(1):46-54 [Non-patent document 8] Gastroenterology.2012;142(1):46~54 pages.e42;quiz e30 [Non-Patent Document 9] Sandler RS, Everhart JE, Donowitz M, et al. Gastroenterology, 2002;122(5):1500~11 [Non-Patent Document 10] Dignass A, Eliakim R, Magro F, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 1:definitions and diagnosis.J Crohn's Colitis.2012;6(10):965-90 [Non-Patent Document 11] Rutter M, Saunders B, Wilkinson K, et al. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology, 2004;126(2):451-9 [Non-Patent Document 12] Truelove SC, Witts LJ.Cortisone and corticotrophin in ulcerative colitis.Br Med J.1959;1(5119):387-94. [Non-Patent Document 13] Kornbluth A, Sachar DB;Practice Parameters Committee of the American College of Gastroenterology.Ulcerative colitis practice guidelines in adults:American College of Gastroenterology, Practice Parameters Committee.Am J Gastroenterol.2010;105(3):501-23;quiz 524 [Non-Patent Document 14] Beaugerie L, Brousse N, Bouvier AM, et al. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet.2009;374(9701):1617-25 [Non-Patent Document 15] Aratari A, Papi C, Clemente V, et al. Colectomy rate in acute severe ulcerative colitis in the infliximab era. Dig Liver Dis. 2008;40(10):821~6 [Non-Patent Document 16] Turner D, Walsh CM, Steinhart AH, et al. Response to corticosteroids in severe ulcerative colitis: a systematic review of the literature and a meta-regression. Clin Gastroenterol Hepatol. 2007;5(1):103–10 [Non-Patent Document 17] Sandborn WJ.State-of-the-art:immunosuppression and biologic therapy.Dig Dis.2010;28(3):536~42 [Non-Patent Document 18] Rutgeerts P, Sandborn W, Feagan B, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005, 353(23):2462-76 [Non-Patent Document 19] Sandborn WJ, van Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology, 2012, 142(2):257–65 [Non-Patent Document 20] Feagan B, Greenberg G, Wild G, et al. Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin, N.Engl.J.Med.2005, 352(24):2499~507 [Non-Patent Document 21] Sandborn W, Feagan B, Marano C, et al., Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis, Gastroenterology, 2014, 146(1):85~95; quiz e14~5 [Non-Patent Document 22] Dignass A, Van Assche G, Lindsay JO et al., European Crohn's and Colitis Oganization (ECCO), The second European evidence-based consensus on the diagnosis and management of Crohn's disease: current management, J Crohn's Colitis, 2010, 4(1): pp. 28-62 [Non-Patent Document 23] Erratum in:J Crohn's Colitis, 2010, 4(3):353 pages [Non-Patent Document 24] Irving PM, Geary RB, Sparrow MP, et al., Review article: appropriate use of corticosteroids in Crohn's disease, Aliment Pharmacol Ther., 2007, 26(3):313-29. [Non-Patent Document 25] Rutgeerts PJ, Review article: the limitations of corticosteroid therapy in Crohn's disease, Aliment Pharmacol Ther., 2001, 15(10): 1515-25. [Non-Patent Document 26] Siegel et al., Review article:Practical Management of Inflammatory Bowel Disease Patients Taking Immunosuppressants, Aliment Pharmacol Ther., 2005, pp. 22:1-16. [Non-Patent Document 27] Targan SR, Hanauer SB, van Deventer SJ et al., A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease, N.Engl.J.Med., 1997, 337(15):1029-35. [Non-patent document 28] Hanauer SB, Feagan BG, Lichtenstein GR, et al., ACCENT I Study Group, Maintenance infliximab for Crohn's disease: the ACCENT I randomized trial, Lancet, 2002, 359(9317): 1541-9. [Non-Patent Document 29] Hanauer SB, Sandborn WJ, Rutgeerts P, et al., Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial, Gastroenterology, 2007, 132(1):52-65. [Non-Patent Document 30] Colombel JF, Sandborn WJ, Rutgeerts P, et al., Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial, Gastroenterology, 2007, 132(1):52-65. [Non-Patent Document 31] Sandborn WJ, Feagan BG, Stoinov S, et al., PRECISE I Study Investigators, Certolizumab pegol for the treatment of Crohn's disease, N.Engl.J.Med., 2007, 357(3):228-38 [Non-Patent Document 32] Schribeinger S, Khaliq-Kareemi M, Lawrence IC, et al., PRECISE 2 Study Investigators, Maintenance therapy with certolizumab pegol for Crohn's disease, N.Engl.J.Med., 2007, 357(3):239-50 [Non-Patent Document 33] Erratum in:N.Engl.J.Med., 2007, 357(13):1357 [Non-Patent Document 34] Sandborn et al., "Natalizumab induction and maintenance therapy for Crohn's disease," N.Engl.J.Med., 2005, 353(18): 1912-25. [Non-Patent Document 35] Van Assche G, Van Ranst M, Sciot R et al., "Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn's disease", N.Engl.J.Med., 2005, 353(4): pp. 362-8 [Non-Patent Document 36] Rubin et al., Inflammatory Bowel Diseases, 2016, 22 Suppl.1:S42~S43 [Non-Patent Document 37] Sands et al., "Effects of Vedolizumab Induction Therapy for Patients With Crohn's Disease in Whom Tumor Necrosis Factor Antagonist Treatment Failed," Gastroenterology, 2014, 147:618-627. [Non-Patent Document 38] Ther.Adv.Gastroenterology, 2016, Vol. 9(1), pp. 26-36 Summary of the Invention [Problem to be solved by the invention]

[0018] There remains a clear need for additional treatment options for CD for patients who have failed or are intolerant to conventional treatments, as well as anti-TNF-α agents or other biologic therapies. [Means for solving the problem]

[0019] (Summary of the Invention) The present disclosure addresses the above-mentioned needs and provides methods for treating Crohn's disease and ulcerative colitis. In some aspects, the present disclosure provides methods for treating Crohn's disease in patients with moderate to severe active Crohn's disease. In some aspects, the present disclosure provides methods for treating ulcerative colitis in patients with moderate to severe active ulcerative colitis. The patient may have had an inadequate response to, or experienced intolerance to, conventional treatments such as aminosalicylates, corticosteroids, or immunosuppressants, or pretreatment with anti-TNF therapy or another biologic agent. In one embodiment, the patient is an adult with moderate to severe active Crohn's disease who has had an inadequate response to, or is intolerant to, corticosteroids, immunomodulators, or biologic therapy.

[0020] In one embodiment, the disclosure relates to a method of inducing clinical remission of Crohn's disease in a patient, comprising: a) administering to the patient at least one induction dose of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide (upadacitinib), or a pharmaceutically acceptable salt or solid form thereof, comprising 30 to 45 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the method further comprises maintaining clinical remission of Crohn's disease, the method further comprising: b) administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt or solid form thereof after the final induction dose has been administered; and c) administering at least one additional maintenance dose once daily thereafter.

[0021] In another embodiment, the disclosure relates to a method of inducing endoscopic improvement of Crohn's disease in a patient, comprising: a) administering to the patient at least one induction dose of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, comprising 30 to 45 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the method further comprises maintaining endoscopic improvement of Crohn's disease, the method further comprising: b) administering to the patient a first maintenance dose of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, after the final induction dose has been administered, and c) administering at least one additional maintenance dose once daily thereafter.

[0022] In another embodiment, the disclosure relates to a method of inducing clinical remission of Crohn's disease in a patient, comprising: a) administering to the patient at least one induction dose of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the method further comprises maintaining clinical remission of Crohn's disease, the method further comprising: b) administering to the patient a first maintenance dose of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, after the final induction dose has been administered, and c) administering at least one additional maintenance dose once daily thereafter.

[0023] In another embodiment, the disclosure relates to a method of inducing endoscopic remission of Crohn's disease in a patient, comprising: a) administering to the patient at least one induction dose of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the method further comprises maintaining endoscopic remission of Crohn's disease, the method further comprising: b) administering to the patient a first maintenance dose of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, after the final induction dose has been administered, and c) administering at least one additional maintenance dose once daily thereafter.

[0024] In one embodiment, the induction dose comprises 45 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0025] In one embodiment, the patient had an inadequate response to or experienced intolerance to pretreatment with a corticosteroid, immunosuppressant, or biologic agent. In one embodiment, the patient had an inadequate response to or experienced intolerance to pretreatment with an anti-TNF agent. In one embodiment, the patient had moderate to severe active Crohn's disease prior to administration of the induction dose.

[0026] In one embodiment, the induction dose is administered orally to the patient. In one embodiment, the induction dose is administered once daily to the patient.

[0027] In one embodiment, clinical remission is achieved within 16 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, clinical remission is achieved within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0028] In one embodiment, endoscopic improvement is achieved within 16 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, endoscopic improvement is achieved within 12 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0029] In one embodiment, clinical remission is achieved within 16 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, clinical remission is achieved within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0030] In one embodiment, endoscopic remission is achieved within 16 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, endoscopic remission is achieved within 12 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0031] In one embodiment, after administration of at least one induction dose, the patient's Simplified Endoscopic Score for Crohn's Disease (SES-CD) is reduced by more than 50% relative to the patient's baseline SES-CD or is in endoscopic remission. In one embodiment, after administration of at least one induction dose, the patient's Simplified Endoscopic Score for Crohn's Disease (SES-CD) is reduced by at least 2 points relative to the patient's baseline SES-CD. In one embodiment, after administration of at least one induction dose, the patient achieves endoscopic remission. In one embodiment, after administration of at least one induction dose, the patient achieves a clinical response. In one embodiment, the patient achieves a clinical response no more than two weeks after the first induction dose. In one embodiment, after administration of at least one induction dose, the patient achieves a CDAI score of less than 150.

[0032] In one embodiment, the first maintenance dose comprises 15 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the first maintenance dose comprises 30 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0033] In one embodiment, at least one additional maintenance dose comprises 15 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, hi one embodiment, at least one additional maintenance dose comprises 30 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0034] In one embodiment, the first maintenance dose and the at least one additional maintenance dose are administered orally. In one embodiment, the first maintenance dose and the at least one additional maintenance dose are administered once daily.

[0035] In one embodiment, the patient maintains clinical remission. In one embodiment, the patient maintains endoscopic improvement. In one embodiment, the patient maintains endoscopic remission.

[0036] In one embodiment, the patient maintains an Simplified Endoscopic Score for Crohn's Disease (SES-CD) that results in a greater than 50% reduction or endoscopic remission from the patient's baseline SES-CD. In one embodiment, the patient maintains an Simplified Endoscopic Score for Crohn's Disease (SES-CD) that results in at least a 2-point reduction from the patient's baseline SES-CD. In one embodiment, the patient maintains endoscopic remission. In one embodiment, the patient maintains a CDAI score of less than 150. In one embodiment, the patient maintains a clinical response.

[0037] In one embodiment, the patient achieves a CDAI score of less than 150 prior to administration of the first maintenance dose. In one embodiment, the patient achieves a clinical response prior to administration of the first maintenance dose.

[0038] In one embodiment, the induction dose comprises 45 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof and is administered orally once daily, the first maintenance dose comprises 30 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof and is administered orally once daily, and at least one additional maintenance dose comprises 30 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof and is administered orally once daily.

[0039] In one embodiment, the induction dose comprises 45 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof and is administered orally once daily, the first maintenance dose comprises 15 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof and is administered orally once daily, and at least one additional maintenance dose comprises 15 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof and is administered orally once daily.

[0040] In one embodiment, the induction dose is a once-daily dose in a modified release formulation. In one embodiment, the first maintenance dose and the at least one additional maintenance dose are each a once-daily dose in a modified release formulation.

[0041] In one embodiment, the disclosure relates to a method for treating Crohn's disease, comprising administering 15 mg to 45 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, to a patient. In one embodiment, the method comprises administering 15 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the method comprises administering 30 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the method comprises administering 45 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, is orally administered to a patient. In one embodiment, upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, is administered to a patient once daily.

[0042] In one embodiment, the disclosure relates to a method for treating Crohn's disease, comprising: a) administering to a patient at least one induction dose of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the method further comprises: b) administering to the patient a first maintenance dose of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, after the final induction dose has been administered; and c) thereafter administering at least one additional maintenance dose once daily.

[0043] In one such embodiment, the first maintenance dose comprises 15 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the first maintenance dose comprises 30 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the first maintenance dose is administered orally.

[0044] In one embodiment, the at least one additional maintenance dose comprises 15 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the at least one additional maintenance dose comprises 30 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the at least one additional maintenance dose is administered orally.

[0045] In one embodiment, the patient maintains a CDAI score of less than 150.

[0046] In one embodiment, the patient had an inadequate response to or experienced intolerance to pretreatment with a corticosteroid, immunosuppressant, or biologic agent, hi one embodiment, the patient had an inadequate response to or experienced intolerance to pretreatment with an anti-TNF agent.

[0047] In one embodiment, the patient achieves clinical remission after administration of at least one induction dose. In one embodiment, the patient achieves endoscopic improvement after administration of at least one induction dose. In one embodiment, the patient achieves endoscopic remission after administration of at least one induction dose. In one embodiment, the patient achieves a clinical response after administration of at least one induction dose.

[0048] In one embodiment, the induction dose comprises 45 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof and is administered orally once daily, the first maintenance dose comprises 30 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof and is administered orally once daily, and the at least one additional maintenance dose comprises 30 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof and is administered orally once daily.

[0049] In one embodiment, the induction dose comprises 45 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof and is administered orally once daily, the first maintenance dose comprises 15 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof and is administered orally once daily, and the at least one additional maintenance dose comprises 15 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof and is administered orally once daily.

[0050] In one embodiment, the induction dose is a once-daily dose in a modified release formulation. In one embodiment, the first maintenance dose and at least one additional maintenance dose are each a once-daily dose in a modified release formulation. In one embodiment, the patient had moderate to severe active Crohn's disease prior to administration of the induction dose.

[0051] In one embodiment, the disclosure relates to a method of inducing remission in a patient with moderately to severely active Crohn's disease, comprising administering 45 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, to the patient. In one such embodiment, the patient has had an inadequate response to or is intolerant to an aminosalicylate, a corticosteroid, an immunosuppressant, a biologic agent, an anti-TNF agent, or a combination thereof.

[0052] In one embodiment, the disclosure relates to a method of inducing clinical remission in a patient with moderately to severely active Crohn's disease, comprising administering 45 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, to the patient. In one such embodiment, the patient has had an inadequate response to or is intolerant to an aminosalicylate, a corticosteroid, an immunosuppressant, a biologic agent, an anti-TNF agent, or a combination thereof.

[0053] In one embodiment, the disclosure relates to a method of inducing endoscopic improvement in a patient with moderately to severely active Crohn's disease, comprising administering 45 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, to the patient. In one such embodiment, the patient has had an inadequate response to or is intolerant to an aminosalicylate, a corticosteroid, an immunosuppressant, a biologic agent, an anti-TNF agent, or a combination thereof.

[0054] In one embodiment, the disclosure relates to a method of treating a resistant patient with moderately to severely active Crohn's disease, comprising administering 45 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, to the patient. In one such embodiment, clinical remission is induced within 16 weeks after administration of the initial dose of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one such embodiment, endoscopic improvement is induced within 12 weeks or within 16 weeks after administration of the initial dose of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0055] In one embodiment, the induction dose comprises 45 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In another embodiment, the first maintenance dose and / or at least one additional maintenance dose comprises 15 mg to 30 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0056] In one embodiment, the disclosure relates to a method of inducing a clinical response in patients with moderately to severely active ulcerative colitis, comprising: a) administering to the patient at least one induction dose of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one such embodiment, the clinical response is a clinical response in which the patient has a reduction in the rectal bleeding subscore of 1 or more, or a reduction of 2 or more points and 30% or more from baseline in the adapted Mayo score, accompanied by an absolute rectal bleeding subscore of 0 or 1. In another such embodiment, the clinical response is a clinical response in which the patient has a reduction in the rectal bleeding subscore of 1 or more from baseline, or a reduction in the full Mayo score of 3 or more points and 30% or more from baseline, accompanied by an absolute rectal bleeding subscore of 0 or 1.

[0057] In yet another embodiment, the method further comprises maintaining the clinical response, said method further comprising b) administering to the patient a first maintenance dose of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, after the final induction dose has been administered, and c) thereafter administering at least one additional maintenance dose once daily.

[0058] In another embodiment, the induction dose comprises 45 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In another embodiment, the first maintenance dose and / or at least one additional maintenance dose comprises 15 mg to 30 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0059] In one embodiment, the disclosed method is a method of inducing clinical remission of Crohn's disease in a patient, comprising: a) administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof, administered orally once daily for at least 4 weeks, comprising 45 mg of upadacitinib, or 45 mg of free base equivalent of a pharmaceutically acceptable salt thereof; and b) the patient achieves clinical remission within 12 weeks after administration of the first induction dose.

[0060] In one embodiment, clinical remission of Crohn's disease is induced within 4 weeks following administration of the first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

[0061] In one embodiment, the method is a method of inducing a clinical response in Crohn's disease in a patient, comprising: a) orally administering to the patient once daily for at least two weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 45 mg of free base; and b) the patient achieves a clinical response.

[0062] In one embodiment, the clinical response for Crohn's disease is induced within 4 weeks after administration of the first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof. In one embodiment, the clinical response for Crohn's disease is induced within 12 weeks after administration of the first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

[0063] In one embodiment, the method is for inducing endoscopic remission of Crohn's disease in a patient, comprising: a) orally administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 45 mg of free base, once daily for at least 12 weeks; and b) the patient achieves endoscopic remission within 12 weeks after administration of the first induction dose.

[0064] In one embodiment, endoscopic remission of Crohn's disease is induced within 4 weeks after administration of the first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

[0065] In one embodiment, endoscopic remission of Crohn's disease is induced within 12 weeks following administration of a first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

[0066] In one embodiment, the method is a method for inducing an endoscopic response in Crohn's disease in a patient, comprising: a) orally administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 45 mg of free base, once daily for at least 12 weeks; and b) the patient achieves an endoscopic response within 12 weeks after administration of the first induction dose.

[0067] In one embodiment, the Crohn's disease endoscopic response is induced within 12 weeks after administration of a first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

[0068] In one embodiment, the method is a method of inducing corticosteroid-free remission of Crohn's disease in a patient, comprising: a) administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof, administered orally once daily for at least 12 weeks, the induction dose comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, equivalent to 45 mg of free base; and b) the patient achieves steroid-free remission within 4 weeks after administration of the first induction dose.

[0069] In one embodiment, the patient is an adult with moderate to severe active Crohn's disease.

[0070] In one embodiment, the patient experiences a decrease in CDAI of greater than 150 within 12 weeks after administration of the first induction dose.

[0071] In one embodiment, the patient has had an inadequate response to or experienced intolerance to prior treatment with a corticosteroid, immunosuppressant, or biologic agent.

[0072] In one embodiment, the patient had an inadequate response to or experienced intolerance to prior treatment with an anti-TNF agent.

[0073] In one embodiment, the patient has had an inadequate response to or experienced intolerance to infliximab, adalimumab, or certolizumab pegol.

[0074] In one embodiment, the patient has had a diagnosis of Crohn's disease for more than 10 years and has had an inadequate response to or experienced intolerance to one or more prior treatments, hi one embodiment, the prior treatment is selected from the group consisting of corticosteroids, immunosuppressants, antibiotics, and biological therapies.

[0075] In one embodiment, the method comprises a method of inducing and maintaining clinical remission of Crohn's disease in a patient, comprising: a) orally administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof in a free base equivalent amount once daily for at least 4 weeks; b) the patient achieves clinical remission within 12 weeks after administration of the first induction dose; c) after the final induction dose is administered, orally administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof in a free base equivalent amount once daily; d) administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; and e) the patient maintains clinical remission 52 weeks after administration of the first induction dose.

[0076] In one embodiment, the method comprises a method of inducing and maintaining a clinical response in a patient with Crohn's disease, comprising: a) orally administering to the patient an induction dose of 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of free base, once daily for at least two weeks; b) the patient achieves a clinical response within two weeks after administration of the first induction dose; c) after the final induction dose has been administered, orally administering to the patient a first maintenance dose of 30 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 30 mg of free base, once daily; d) administering to the patient at least one additional maintenance dose of upadacitinib, or a pharmaceutically acceptable salt thereof; and e) the patient maintains the clinical response for 52 weeks after administration of the first induction dose.

[0077] In one embodiment, the clinical response in Crohn's disease is induced within 4 weeks of administration of the first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

[0078] In one embodiment, the clinical response in Crohn's disease is induced within 12 weeks of administration of the first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

[0079] In one embodiment, the method comprises a method of inducing and maintaining endoscopic remission of Crohn's disease in a patient, comprising: a) orally administering to the patient an induction dose of 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of free base, once daily for at least 4 weeks; b) the patient achieves endoscopic remission within 12 weeks after administration of the first induction dose; c) after the final induction dose has been administered, orally administering to the patient a first maintenance dose of 30 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 30 mg of free base, once daily; d) administering to the patient at least one additional maintenance dose of upadacitinib, or a pharmaceutically acceptable salt thereof; and e) the patient maintains endoscopic remission 52 weeks after administration of the first induction dose.

[0080] In one embodiment, endoscopic remission of Crohn's disease is induced within 12 weeks following administration of a first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

[0081] In one embodiment, the method is for inducing and maintaining an endoscopic response in a patient for Crohn's disease, comprising: a) orally administering to the patient an induction dose of 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of free base, once daily for at least 4 weeks; b) the patient achieves an endoscopic response within 4 weeks after administration of the first induction dose; c) after the final induction dose has been administered, orally administering to the patient a first maintenance dose of 30 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 30 mg of free base, once daily; d) administering to the patient at least one additional maintenance dose of upadacitinib, or a pharmaceutically acceptable salt thereof; and e) the patient maintains an endoscopic response for 52 weeks after administration of the first induction dose.

[0082] In one embodiment, the Crohn's disease endoscopic response is induced within 12 weeks after administration of a first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

[0083] In one embodiment, the method is for inducing and maintaining corticosteroid-free remission of Crohn's disease in a patient, comprising: a) orally administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof once daily for at least 12 weeks; b) the patient achieves steroid-free remission within 4 weeks after administration of the first induction dose; and c) administering to the patient a final induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof once daily for at least 12 weeks. after administration of the first induction dose, orally administering to the patient once daily a first maintenance dose comprising 30 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 30 mg of free base; d) administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; and e) the patient maintains corticosteroid-free remission for 52 weeks after administration of the first induction dose.

[0084] In one embodiment, the patient is an adult with moderate to severe active Crohn's disease.

[0085] In one embodiment, the patient experiences an improvement in stool frequency one week after the first induction dose. In one embodiment, the patient experiences an improvement in abdominal pain eight weeks after the first induction dose.

[0086] In one embodiment, the patient experiences a decrease in CDAI of greater than 150 within 12 weeks after administration of the first induction dose.

[0087] In one embodiment, the patient has had an inadequate response to or experienced intolerance to prior treatment with a corticosteroid, immunosuppressant, or biologic agent.

[0088] In one embodiment, the patient had an inadequate response to or experienced intolerance to prior treatment with an anti-TNF agent.

[0089] In one embodiment, the anti-TNF agent is infliximab, adalimumab, or certolizumab pegol.

[0090] In one embodiment, the patient has had a diagnosis of Crohn's disease for more than 10 years, has had an inadequate response to prior treatment, or has experienced intolerance.

[0091] In one embodiment, the conditioning treatment is selected from corticosteroids, immunosuppressants, antibiotics, and biological therapies.

[0092] In one embodiment, the method is a method of inducing and maintaining clinical remission of Crohn's disease in a patient, comprising: a) orally administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof in a free base equivalent amount once daily for at least 4 weeks; b) the patient achieves clinical remission within 4 weeks after administration of the first induction dose; c) after the final induction dose is administered, orally administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof in a free base equivalent amount once daily; d) administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; and e) the patient maintains clinical remission for 52 weeks after administration of the first induction dose.

[0093] In one embodiment, the method is for inducing and maintaining a clinical response in a patient with Crohn's disease, comprising: a) orally administering to the patient an induction dose of 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of free base, once daily for at least two weeks; b) the patient achieves a clinical response within two weeks after administration of the first induction dose; c) after the final induction dose has been administered, orally administering to the patient a first maintenance dose of 15 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 15 mg of free base, once daily; d) administering to the patient at least one additional maintenance dose of upadacitinib, or a pharmaceutically acceptable salt thereof; and e) the patient maintains the clinical response for 52 weeks after administration of the first induction dose.

[0094] In one embodiment, the clinical response in Crohn's disease is induced within 4 weeks of administration of the first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

[0095] In one embodiment, the clinical response in Crohn's disease is induced within 12 weeks of administration of the first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

[0096] In one embodiment, the method is for inducing and maintaining endoscopic remission of Crohn's disease in a patient, comprising: a) orally administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 45 mg of free base, once daily for at least 4 weeks; b) the patient achieves endoscopic remission within 4 weeks after administration of the first induction dose; c) after the final induction dose has been administered, orally administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 15 mg of free base, once daily; d) administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; and e) the patient maintains endoscopic remission for 52 weeks after administration of the first induction dose.

[0097] In one embodiment, the method is for inducing and maintaining endoscopic remission of Crohn's disease in a patient, comprising: a) orally administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 45 mg of free base, once daily for at least 12 weeks; b) the patient achieves endoscopic remission within 4 weeks after administration of the first induction dose; c) after the final induction dose has been administered, orally administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 15 mg of free base, once daily; d) administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; and e) the patient maintains endoscopic remission for 52 weeks after administration of the first induction dose.

[0098] In one embodiment, endoscopic remission of Crohn's disease is induced within 12 weeks following administration of a first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

[0099] In one embodiment, the method is for inducing and maintaining an endoscopic response in a patient for Crohn's disease, comprising: a) orally administering to the patient an induction dose of 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of free base, once daily for at least 4 weeks; b) the patient achieves an endoscopic response within 4 weeks after administration of the first induction dose; c) after the final induction dose has been administered, orally administering to the patient a first maintenance dose of 15 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 15 mg of free base, once daily; d) administering to the patient at least one additional maintenance dose of upadacitinib, or a pharmaceutically acceptable salt thereof; and e) the patient maintains an endoscopic response for 52 weeks after administration of the first induction dose.

[0100] In one embodiment, the Crohn's disease endoscopic response is induced within 12 weeks after administration of a first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

[0101] In one embodiment, the method is for inducing and maintaining corticosteroid-free remission of Crohn's disease in a patient, comprising: a) orally administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof once daily for at least 12 weeks; b) the patient achieves steroid-free remission within 12 weeks after administration of the first induction dose; and c) administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof once daily for at least 12 weeks. after administration of the first induction dose, orally administering to the patient once daily a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 15 mg of upadacitinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 15 mg of free base; d) administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; and e) the patient maintains corticosteroid-free remission for 52 weeks after administration of the first induction dose.

[0102] In one embodiment, the patient is an adult with moderate to severe active Crohn's disease.

[0103] In one embodiment, the patient experiences a decrease in CDAI of >150 within 12 weeks after administration of the first induction dose.

[0104] In one embodiment, the patient has had an inadequate response to or experienced intolerance to prior treatment with a corticosteroid, immunosuppressant, or biologic agent.

[0105] In one embodiment, the patient had an inadequate response to or experienced intolerance to prior treatment with an anti-TNF agent.

[0106] In one embodiment, the patient has had an inadequate response to or experienced intolerance to prior treatment with an anti-TNF agent that is infliximab, adalimumab, or certolizumab pegol.

[0107] In one embodiment, the patient has had a diagnosis of Crohn's disease for more than 10 years and has had an inadequate response to or experienced intolerance to one or more prior treatments.

[0108] In one embodiment, the method includes a method wherein the pretreatment is selected from a corticosteroid, an immunomodulator, an antibiotic, and a biological therapy.

[0109] In one embodiment, the method comprises a method of inducing clinical remission of ulcerative colitis in a patient, comprising: a) orally administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof in a free base equivalent amount once daily for at least 4 weeks; and b) the patient achieves clinical remission within 4 weeks after administration of the first induction dose.

[0110] In one embodiment, the method comprises a method of inducing clinical remission of ulcerative colitis in a patient, comprising: a) orally administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof, once daily for at least 6 weeks, the induction dose comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof, equivalent to 45 mg of free base; and b) the patient achieves clinical remission within 6 weeks after administration of the first 45 mg induction dose.

[0111] In one embodiment, the method comprises a method of inducing clinical remission of ulcerative colitis in a patient, comprising: a) orally administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof, once daily for at least 8 weeks, the induction dose comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof, equivalent to 45 mg of free base; and b) the patient achieves clinical remission within 8 weeks after administration of the first 45 mg induction dose.

[0112] In one embodiment, the method comprises a method of inducing endoscopic improvement of ulcerative colitis in a patient, comprising: a) orally administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof in a free base equivalent amount once daily for at least 8 weeks; and b) the patient achieves endoscopic improvement within 8 weeks after administration of the first induction dose.

[0113] In one embodiment, the method comprises a method of inducing endoscopic remission of ulcerative colitis in a patient, comprising: a) orally administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof, once daily for at least 8 weeks; and b) the patient achieves endoscopic remission within 8 weeks after administration of the first 45 mg induction dose.

[0114] In one embodiment, the patient has moderate to severe active ulcerative colitis.

[0115] In one embodiment, the patient is taking a corticosteroid at the time of the first induction dose.

[0116] In one embodiment, corticosteroids are not used in clinical remission, endoscopic improvement, or endoscopic remission.

[0117] In one embodiment, the patient has demonstrated an inadequate response, loss of response, or intolerance to one or more corticosteroids, immunosuppressants, or biologic therapies.

[0118] In one embodiment, the immunosuppressant is selected from oral azathioprine, 6-mercaptopurine, injectable methotrexate, and tacrolimus.

[0119] In one embodiment, the biologic therapy is selected from infliximab, adalimumab, golimumab, and vedolizumab.

[0120] In one embodiment, an inadequate response in a patient taking corticosteroids is defined as a patient experiencing persistently active signs and symptoms of disease despite a history of at least one induction regimen that included prednisone ≥ 40 mg / day equivalent orally for 3-4 weeks or intravenously for 1 week.

[0121] In one embodiment, the patient is unable to taper the corticosteroid to less than 10 mg prednisone equivalent orally daily without recurrence of active disease.

[0122] In one embodiment, the patient's intolerance to corticocosteroids results in Cushing's syndrome, osteopenia, osteoporosis, hyperglycemia, insomnia, or infection.

[0123] In one embodiment, patients experiencing an inadequate response to immunosuppressants have experienced signs and symptoms of persistently active disease despite a history of at least one 90-day regimen of oral azathioprine, 6-mercaptopurine, injectable methotrexate, or tacrolimus.

[0124] In one embodiment, the patient experiencing an inadequate response to the immunosuppressant experienced nausea, vomiting, abdominal pain, pancreatitis, liver enzyme abnormalities, lymphopenia, or infection.

[0125] In one embodiment, patients experiencing an inadequate response to biologic therapy experienced signs and symptoms of persistently active disease despite a history of: a) at least one 6-week induction regimen of infliximab comprising intravenous doses of ≧5 mg / kg at weeks 0, 2, and 6; b) at least one 4-week induction regimen of adalimumab comprising one subcutaneous dose of 160 mg followed by one subcutaneous dose of 80 mg or one subcutaneous dose of 80 mg followed by one subcutaneous dose of 40 mg, at least two weeks apart; c) at least one 2-week induction regimen of golimumab comprising one subcutaneous dose of 200 mg followed by one subcutaneous dose of 100 mg, at least two weeks apart; d) at least one 6-week induction regimen of vedolizumab comprising intravenous doses of 300 mg at weeks 0, 2, and 6.

[0126] In one embodiment, the patient experiencing an inadequate response to biologic therapy experienced a recurrence of symptoms during maintenance dosing planned according to previous clinical benefit.

[0127] In one embodiment, the patient experiencing intolerance to the biologic therapy has experienced an infusion reaction, demyelination, congestive heart failure, or infection.

[0128] In one embodiment, the method is for inducing and maintaining clinical remission of ulcerative colitis in a patient, comprising: a) orally administering to the patient an induction dose of 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of free base, once daily for at least 4 weeks; b) the patient achieves clinical remission within 4 weeks after administration of the first induction dose; and b) after the final induction dose has been administered, orally administering to the patient a first maintenance dose of 30 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 30 mg of free base, once daily; d) administering to the patient at least one additional maintenance dose of upadacitinib, or a pharmaceutically acceptable salt thereof; and e) the patient maintains clinical remission for 52 weeks after administration of the first induction dose.

[0129] In one embodiment, the method is for inducing and maintaining clinical remission of ulcerative colitis in a patient, comprising: a) orally administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof once daily for at least 6 weeks; b) the patient achieves clinical remission within 6 weeks after administration of the first 45 mg induction dose; and c) the patient achieves clinical remission within 6 weeks after administration of the final 45 mg induction dose. after administration of the first induction dose, orally administering to the patient once daily a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 30 mg of upadacitinib or a pharmaceutically acceptable salt thereof in a free base equivalent amount; d) administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; and e) the patient maintains clinical remission for 52 weeks after administration of the first induction dose.

[0130] In one embodiment, the method is for inducing and maintaining clinical remission of ulcerative colitis in a patient, comprising: a) orally administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof once daily for at least 8 weeks; b) the patient achieves clinical remission within 8 weeks after administration of the first 45 mg induction dose; and c) the patient achieves clinical remission within 8 weeks after administration of the final 45 mg induction dose. after administration of the first induction dose, orally administering to the patient once daily a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 30 mg of upadacitinib or a pharmaceutically acceptable salt thereof in a free base equivalent amount; d) administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; and e) the patient maintains clinical remission for 52 weeks after administration of the first induction dose.

[0131] In one embodiment, the method is for inducing and maintaining endoscopic improvement of ulcerative colitis in a patient, comprising: a) orally administering to the patient an induction dose of 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of free base, once daily for at least 8 weeks; b) the patient achieves endoscopic improvement within 8 weeks after administration of the first induction dose; c) after the final induction dose has been administered, orally administering to the patient a first maintenance dose of 30 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 30 mg of free base, once daily; d) administering to the patient at least one additional maintenance dose of upadacitinib, or a pharmaceutically acceptable salt thereof; and e) the patient maintains clinical remission 52 weeks after administration of the first induction dose.

[0132] In one embodiment, the method is for inducing and maintaining endoscopic remission of ulcerative colitis in a patient, comprising: a) orally administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof once daily for at least 8 weeks; b) the patient achieves endoscopic remission within 8 weeks after administration of the first 45 mg induction dose; and c) the final induction dose is and (d) administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof, wherein the patient maintains clinical remission for 52 weeks after administration of the first induction dose.

[0133] In one embodiment, the method is for inducing and maintaining endoscopic remission of ulcerative colitis in a patient, comprising: a) orally administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof once daily for at least 8 weeks; b) the patient achieves endoscopic remission within 8 weeks after administration of the first 45 mg induction dose; and c) the final induction dose is and (d) administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof, wherein the first maintenance dose is 15 mg of upadacitinib or a pharmaceutically acceptable salt thereof once daily, the first maintenance dose comprising 15 mg of upadacitinib or a pharmaceutically acceptable salt thereof equivalent to 15 mg of free base; and (e) the patient maintains clinical remission for 52 weeks after administration of the first induction dose.

[0134] In one embodiment, the patient has moderately to severely active ulcerative colitis. In one embodiment, the patient is an adult. In one embodiment, the patient has had an inadequate response to corticosteroids, immunomodulators, or biological therapy. In one embodiment, the patient has lost response to aminosalicylate, corticosteroids, immunomodulators, or biological therapy. In one embodiment, the patient is intolerant to corticosteroids, immunomodulators, or biological therapy. In one embodiment, the patient is an adult and has moderately to severely active ulcerative colitis and has had an inadequate response, lost response, or is intolerant to aminosalicylate, corticosteroids, immunomodulators (IMMs), or biological therapy.

[0135] In one embodiment, the patient is taking a corticosteroid at the time of the first induction dose.

[0136] In one embodiment, corticosteroids are not used in clinical remission, endoscopic improvement, or endoscopic remission.

[0137] In one embodiment, the patient has demonstrated an inadequate response, loss of response, or intolerance to one or more corticosteroids, immunosuppressants, or biologic therapies.

[0138] In one embodiment, the immunosuppressant is selected from oral azathioprine, 6-mercaptopurine, injectable methotrexate, and tacrolimus.

[0139] In one embodiment, the biologic therapy is selected from infliximab, adalimumab, golimumab, and vedolizumab.

[0140] In one embodiment, an inadequate response in a patient taking corticosteroids is defined as a patient experiencing persistently active signs and symptoms of disease despite a history of at least one induction regimen that included prednisone ≥ 40 mg / day equivalent orally for 3-4 weeks or intravenously for 1 week.

[0141] In one embodiment, the patient is unable to taper the corticosteroid to less than 10 mg prednisone equivalent orally daily without recurrence of active disease.

[0142] In one embodiment, the patient's intolerance to corticosteroids results in Cushing's syndrome, osteopenia, osteoporosis, hyperglycemia, insomnia, or infection.

[0143] In one embodiment, patients experiencing an inadequate response to immunosuppressants have experienced signs and symptoms of persistently active disease despite a history of at least one 90-day regimen of oral azathioprine, 6-mercaptopurine, injectable methotrexate, or tacrolimus.

[0144] In one embodiment, the patient experiencing an inadequate response to the immunosuppressant experienced nausea, vomiting, abdominal pain, pancreatitis, liver enzyme abnormalities, lymphopenia, or infection.

[0145] In one embodiment, patients with ulcerative colitis or Crohn's disease who have experienced an inadequate response to biologic therapy have experienced signs and symptoms of persistently active disease despite a history of: a) at least one 6-week induction regimen of infliximab comprising intravenous doses of ≧5 mg / kg at weeks 0, 2, and 6; b) at least one 4-week induction regimen of adalimumab comprising one subcutaneous dose of 160 mg followed by one subcutaneous dose of 80 mg, or one subcutaneous dose of 80 mg followed by one subcutaneous dose of 40 mg, at least two weeks apart; c) at least one 2-week induction regimen of golimumab comprising one subcutaneous dose of 200 mg followed by one subcutaneous dose of 100 mg, at least two weeks apart; d) at least one 6-week induction regimen of vedolizumab comprising intravenous doses of 300 mg at weeks 0, 2, and 6.

[0146] In one embodiment, the patient experiencing an inadequate response to biologic therapy experienced a recurrence of symptoms during maintenance dosing planned according to previous clinical benefit.

[0147] In one embodiment, the patient experiencing intolerance to the biologic therapy has experienced an infusion reaction, demyelination, congestive heart failure, or infection.

[0148] In one embodiment, the method is a method of inducing and maintaining clinical remission of ulcerative colitis in a patient, comprising: a) orally administering to the patient an induction dose of 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of free base, once daily for at least 4 weeks; b) the patient achieves clinical remission within 4 weeks after administration of the first induction dose; c) after the final induction dose has been administered, orally administering to the patient a first maintenance dose of 15 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 15 mg of free base, once daily; d) administering to the patient at least one additional maintenance dose of upadacitinib, or a pharmaceutically acceptable salt thereof; and e) the patient maintains clinical remission for 52 weeks after administration of the first induction dose.

[0149] In one embodiment, the method is for inducing and maintaining clinical remission of ulcerative colitis in a patient, comprising: a) orally administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof once daily for at least 6 weeks; b) the patient achieves clinical remission within 6 weeks after administration of the first 45 mg induction dose; and c) the patient achieves clinical remission within 6 weeks after administration of the final 45 mg induction dose. following administration of the first induction dose, orally administering to the patient once daily a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 15 mg of upadacitinib or a pharmaceutically acceptable salt thereof in a free base equivalent amount; d) administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; and e) the patient maintains clinical remission for 52 weeks after administration of the first induction dose.

[0150] In one embodiment, the method is for inducing and maintaining clinical remission of ulcerative colitis in a patient, comprising: a) orally administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof once daily for at least 8 weeks; b) the patient achieves clinical remission within 8 weeks after administration of the first 45 mg induction dose; and c) the patient achieves clinical remission within 8 weeks after administration of the final 45 mg induction dose. following administration of the first induction dose, orally administering to the patient once daily a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 15 mg of upadacitinib or a pharmaceutically acceptable salt thereof in a free base equivalent amount; d) administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; and e) the patient maintains clinical remission for 52 weeks after administration of the first induction dose.

[0151] In one embodiment, the method is for inducing and maintaining endoscopic improvement of ulcerative colitis in a patient, comprising: a) orally administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 45 mg of free base, once daily for at least 8 weeks; b) the patient achieves endoscopic improvement within 8 weeks after administration of the first induction dose; c) after the final induction dose has been administered, orally administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 15 mg of free base, once daily; d) administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; and e) the patient maintains clinical remission 52 weeks after administration of the first induction dose.

[0152] In one embodiment, the method is for inducing and maintaining endoscopic remission of ulcerative colitis in a patient, comprising: a) orally administering to the patient an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib or a pharmaceutically acceptable salt thereof once daily for at least 8 weeks; b) the patient achieves endoscopic remission within 8 weeks after administration of the first 45 mg induction dose; and c) the final induction dose is the method further comprising: (a) administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof orally once daily, after administration of the first induction dose, the first maintenance dose comprising 15 mg of upadacitinib or a pharmaceutically acceptable salt thereof equivalent to 15 mg of free base; (b) administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; and (c) the patient maintaining clinical remission for 52 weeks after administration of the first induction dose.

[0153] In one embodiment, the patient has moderate to severe active ulcerative colitis.

[0154] In one embodiment, the patient is taking a corticosteroid at the time of the first induction dose.

[0155] In one embodiment, corticosteroids are not used in clinical remission, endoscopic improvement, or endoscopic remission.

[0156] In one embodiment, the patient has demonstrated an inadequate response, loss of response, or intolerance to one or more corticosteroids, immunosuppressants, or biologic therapies.

[0157] In one embodiment, the immunosuppressant is selected from oral azathioprine, 6-mercaptopurine, injectable methotrexate, and tacrolimus.

[0158] In one embodiment, the biologic therapy is selected from infliximab, adalimumab, golimumab, and vedolizumab.

[0159] In one embodiment, an inadequate response in a patient taking corticosteroids is defined as a patient experiencing persistently active signs and symptoms of disease despite a history of at least one induction regimen that included prednisone ≥ 40 mg / day equivalent orally for 3-4 weeks or intravenously for 1 week.

[0160] In one embodiment, the patient is unable to taper the corticosteroid to less than 10 mg prednisone equivalent orally daily without recurrence of active disease.

[0161] In one embodiment, the patient's intolerance to corticosteroids results in Cushing's syndrome, osteopenia, osteoporosis, hyperglycemia, insomnia, or infection.

[0162] In one embodiment, patients experiencing an inadequate response to immunosuppressants have experienced signs and symptoms of persistently active disease despite a history of at least one 90-day regimen of oral azathioprine, 6-mercaptopurine, injectable methotrexate, or tacrolimus.

[0163] In one embodiment, the patient experiencing intolerance to the immunosuppressant experienced nausea, vomiting, abdominal pain, pancreatitis, liver enzyme abnormalities, lymphopenia, or infection.

[0164] In one embodiment, patients experiencing an inadequate response to biologic therapy experienced signs and symptoms of persistently active disease despite a history of: a) at least one 6-week induction regimen of infliximab comprising intravenous doses of ≧5 mg / kg at weeks 0, 2, and 6; b) at least one 4-week induction regimen of adalimumab comprising one subcutaneous dose of 160 mg followed by one subcutaneous dose of 80 mg or one subcutaneous dose of 80 mg followed by one subcutaneous dose of 40 mg, at least two weeks apart; c) at least one 2-week induction regimen of golimumab comprising one subcutaneous dose of 200 mg followed by one subcutaneous dose of 100 mg, at least two weeks apart; d) at least one 6-week induction regimen of vedolizumab comprising intravenous doses of 300 mg at weeks 0, 2, and 6.

[0165] In one embodiment, the patient experiencing an inadequate response to biologic therapy experienced a recurrence of symptoms during maintenance dosing planned according to previous clinical benefit.

[0166] In one embodiment, the patient experiencing intolerance to the biologic therapy has experienced an infusion reaction, demyelination, congestive heart failure, or infection. [Brief explanation of the drawings]

[0167] [Figure 1] FIG. 1 is a schematic diagram of the study design for the clinical study described in Example 8. [Figure 2] FIG. 1 is a schematic diagram of the 36-week extension phase for the clinical study described in Example 8. Patients who did not respond adequately during the double-blind portion of the extension phase were eligible to receive open-label treatment. [Figure 3A] 1 is a graph showing the relationship between upadacitinib plasma concentrations and clinical response (Week 16) as determined in the clinical study of Example 8. Arrows indicate median exposure (mg) per immediate-release dose. Maximum and minimum plasma concentrations per exposure bottle are indicated in parentheses. [Figure 3B]1 is a graph showing the relationship between upadacitinib plasma concentrations and (NRI) clinical remission (Week 16) as determined in the clinical study of Example 8. Arrows indicate median exposure (mg) per immediate-release dose. Maximum and minimum plasma concentrations per exposure bottle are indicated in parentheses. [Figure 3C] 1 is a graph showing the relationship between upadacitinib plasma concentrations and controlled clinical remission (week 16) as determined in the clinical study of Example 8. Arrows indicate median exposure (mg) per immediate-release dose. Maximum and minimum plasma concentrations per exposure bottle are indicated in parentheses. [Figure 3D] 1 is a graph showing the relationship between upadacitinib plasma concentrations and CDAI reduction of ≧70 (Week 16) as determined in the clinical study of Example 8. Arrows indicate median exposure (mg) per immediate-release dose. Maximum and minimum plasma concentrations per exposure bottle are indicated in parentheses. [Figure 3E] 1 is a graph showing the relationship between upadacitinib plasma concentrations and CDAI reduction > 100 (Week 16) as determined in the clinical study of Example 8. Arrows indicate median exposure (mg) per immediate-release dose. Maximum and minimum plasma concentrations per exposure bottle are indicated in parentheses. [Figure 3F] 1 is a graph showing the relationship between upadacitinib plasma concentrations and CDAI<150 (Week 16) as determined in the clinical study of Example 8. Arrows indicate median exposure (mg) per immediate-release dose. Maximum and minimum plasma concentrations per exposure bottle are indicated in parentheses. [Figure 3G] 1 is a graph showing the relationship between upadacitinib plasma concentrations and endoscopic response (at Week 12 or Week 16) as determined in the clinical study of Example 8. Arrows indicate median exposure (mg) per immediate-release dose. Maximum and minimum plasma concentrations per exposure bottle are indicated in parentheses. [Figure 3H] 1 is a graph showing the relationship between upadacitinib plasma concentrations and endoscopic improvement (Week 16) as determined in the clinical study of Example 8. Arrows indicate median exposure (mg) per immediate-release dose. Maximum and minimum plasma concentrations per exposure bottle are shown in parentheses. [Figure 3I]1 is a graph showing the relationship between upadacitinib plasma concentrations and endoscopic remission (at Week 12 or Week 16) as determined in the clinical study of Example 8. Arrows indicate median exposure (mg) per immediate-release dose. Maximum and minimum plasma concentrations per exposure bottle are indicated in parentheses. [Figure 4AB] 1 is a graph showing model-predicted efficacy (NRI) of different upadacitinib doses for the immediate-release (IR) BID formulation or the modified-release (MR) QD formulation (simulating 200 patients / group) at weeks 12 or 16. Predicted outcomes are based on the exposure-response relationship as determined in the study of Example 8. [Figure 4CD] 1 is a graph showing model-predicted efficacy (NRI) of different upadacitinib doses for the immediate-release (IR) BID formulation or the modified-release (MR) QD formulation (simulating 200 patients / group) at weeks 12 or 16. Predicted results are based on exposure-response relationships as determined in the study of Example 8. [Figure 4E] 1 is a graph showing model-predicted efficacy (NRI) of different upadacitinib doses for the immediate-release (IR) BID formulation or the modified-release (MR) QD formulation (simulating 200 patients / group) at weeks 12 or 16. Predicted results are based on exposure-response relationships as determined in the study of Example 8. [Figure 4F] 1 is a graph showing model-predicted efficacy (NRI) of different upadacitinib doses for the immediate-release (IR) BID formulation or the modified-release (MR) QD formulation (simulating 200 patients / group) at weeks 12 or 16. Predicted results are based on exposure-response relationships as determined in the study of Example 8. [Figure 5A] Figure 1 shows the relationship between upadacitinib plasma concentrations and change from baseline for selected measured laboratory parameters at Week 16 (LOCF) of the clinical study in Example 8. Maximum and minimum plasma concentrations for each data point are shown in parentheses. [Figure 5B]Figure 1 shows the relationship between upadacitinib plasma concentrations and change from baseline for selected measured laboratory parameters at Week 16 (LOCF) of the clinical study in Example 8. Maximum and minimum plasma concentrations for each data point are shown in parentheses. [Figure 5C] Figure 1 shows the relationship between upadacitinib plasma concentrations and change from baseline for selected measured laboratory parameters at Week 16 (LOCF) of the clinical study in Example 8. Maximum and minimum plasma concentrations for each data point are shown in parentheses. [Figure 5D] Figure 1 shows the relationship between upadacitinib plasma concentrations and change from baseline for selected measured laboratory parameters at Week 16 (LOCF) of the clinical study in Example 8. Maximum and minimum plasma concentrations for each data point are shown in parentheses. [Figure 5E] Figure 1 shows the relationship between upadacitinib plasma concentrations and change from baseline for selected measured laboratory parameters at Week 16 (LOCF) of the clinical study in Example 8. Maximum and minimum plasma concentrations for each data point are shown in parentheses. [Figure 5F] Figure 1 shows the relationship between upadacitinib plasma concentrations and change from baseline for selected measured laboratory parameters at Week 16 (LOCF) of the clinical study in Example 8. Maximum and minimum plasma concentrations for each data point are shown in parentheses. [Figure 5G] Figure 1 shows the relationship between upadacitinib plasma concentrations and change from baseline for selected measured laboratory parameters at Week 16 (LOCF) of the clinical study in Example 8. Maximum and minimum plasma concentrations for each data point are shown in parentheses. [Figure 5H] Figure 1 shows the relationship between upadacitinib plasma concentrations and change from baseline for selected measured laboratory parameters at Week 16 (LOCF) of the clinical study in Example 8. Maximum and minimum plasma concentrations for each data point are shown in parentheses. [Figure 6]1 is a graph showing the percentage of subjects achieving clinical response or clinical remission at week 12 of the study of Example 8. Results are shown for subjects who were steroid-naive at baseline. [Figure 7] Figure 1 shows the mean plasma concentrations of upadacitinib over time after 7 days of administration under fasting conditions of 6 mg twice-daily immediate-release capsules (Regimen K) or 15 mg once-daily modified-release tablets (Regimen L). [Figure 8] Figure 1 shows the mean plasma concentrations of upadacitinib over time after 7 days of administration under fasting conditions of 12 mg twice-daily immediate-release capsules (Regimen M) or 30 mg once-daily modified-release tablets (Regimen N). [Figure 9] 1 shows clinical remission and endoscopic responses in a resistant patient population administered upadacitinib or placebo in the Crohn's disease clinical study of Example 8. [Figure 10A] 1 is a graph showing the percentage of subjects who achieved controlled clinical remission at week 2 of the study of Example 8. [Figure 10B] 1 is a graph showing the percentage of subjects who achieved controlled clinical remission at week 4 of the study of Example 8. [Figure 10C] 1 is a graph showing the percentage of subjects who achieved controlled clinical remission at week 8 of the study of Example 8. [Figure 10D] 1 is a graph showing the percentage of subjects who achieved controlled clinical remission at week 12 of the study of Example 8. [Figure 10E] 1 is a graph showing the percentage of subjects who achieved controlled clinical remission at week 16 of the study of Example 8. [Figure 11A] 1 is a graph showing the percentage of subjects achieving an enhanced clinical response at week 2 of the study of Example 8. [Figure 11B] 1 is a graph showing the percentage of subjects achieving an enhanced clinical response at week 4 of the study of Example 8. [Figure 11C]1 is a graph showing the percentage of subjects achieving an enhanced clinical response at week 8 of the study of Example 8. [Figure 11D] 1 is a graph showing the percentage of subjects achieving an enhanced clinical response at week 12 of the study of Example 8. [Figure 11E] FIG. 11E is a graph showing the percentage of subjects achieving an enhanced clinical response at week 16 of the study of Example 8 (FIG. 11E). [Figure 12] 1 shows the mean change in hs-CRP (percentage above baseline) over time (weeks) after 16 weeks of upadacitinib treatment with placebo (PBO), 3, 6, 12, 24 mg twice daily (BID), and 24 mg once daily (QD). Adjusted clinical remission was analyzed in patients with a baseline SF≧4 and AP≧2.0. [Figure 13] FIG. 1 is a schematic diagram of the study design for the ulcerative colitis clinical study described in Example 12. [Figure 14] FIG. 1 is a schematic diagram illustrating one method for preparing the amorphous free base. [Figure 15] FIG. 1 is a schematic diagram illustrating one method of preparing free base hydrate Form C. [Figure 16] FIG. 1 is a schematic diagram illustrating one method for preparing tartrate salt hydrate. [Figure 17A] 1 is a powder X-ray diffraction pattern corresponding to the amorphous free base (via precipitation). [Figure 17B] 1 is a powder X-ray diffraction pattern corresponding to the amorphous free base (via dehydration). [Figure 18] 1 is a powder X-ray diffraction pattern corresponding to the free base solvate form A (isopropyl acetate / water solvate). [Figure 19] 1 is a powder X-ray diffraction pattern corresponding to free base hydrate form B. [Figure 20] 1 is a powder X-ray diffraction pattern corresponding to free base hydrate form C. [Figure 21]

[0023] Figure 12 is a powder X-ray diffraction pattern corresponding to the tartrate salt hydrate. The experimental PXRD pattern is shown below and the calculated PXRD pattern is shown above. [Figure 22] 1 is a powder X-ray diffraction pattern corresponding to free base anhydrous Form D. [Figure 23] 23A and 23B are graphs showing the predicted efficacy of exposure-response models for clinical and endoscopic endpoints for the QD regimen of extended-release formulations. Figure 23A shows the percentage of subjects predicted to achieve clinical response at week 12, Figure 23B shows the percentage of subjects predicted to achieve adjusted clinical remission at week 12, Figure 23C shows the percentage of subjects predicted to achieve CDAI remission at week 12, Figure 23D shows the percentage of subjects predicted to achieve endoscopic response at weeks 12 / 16, Figure 23E shows the percentage of subjects predicted to achieve endoscopic improvement at weeks 12 / 16, and Figure 23F shows the percentage of subjects predicted to achieve endoscopic remission at weeks 12 / 16. DETAILED DESCRIPTION OF THE INVENTION

[0168] This written description uses examples to disclose the present disclosure and to enable one of ordinary skill in the art to practice the invention, including making and using any of the disclosed compositions and performing any of the disclosed methods or processes. The patentable scope of the invention is defined by the claims and may include other examples that occur to those of ordinary skill in the art. Such other examples are contemplated as being within the scope of the claims if they contain elements that are no different from the literal language of the claims or if they contain equivalent elements.

[0169] I. Definition The section headings used in this section and throughout this disclosure are not intended to be limiting.

[0170] Where a range of numerical values ​​is recited, each intervening number within the range is expressly intended to be of the same precision. For example, in the range 6 to 9, the numbers 7 and 8 are also contemplated in addition to 6 and 9, and in the range 6.0 to 7.0, the numbers 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, and 7.0 are expressly intended. Similarly, all ratios recited include all subratios within the broader ratio.

[0171] The singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0172] The term "about" generally refers to a range of numbers that one of ordinary skill in the art would consider equivalent to the recited value (i.e., having the same function or result). In many instances, the term "about" may include numbers that are rounded to the nearest significant figure.

[0173] The term "adapted Mayo" or "adapted Mayo score," when used in connection with ulcerative colitis, refers to the Mayo scoring system for assessment of ulcerative colitis activity, excluding the Physician Global Assessment subscore.

[0174] The term "adult" refers to a person aged 16 or over.

[0175] The abbreviation "AE" refers to adverse events.

[0176] The term "alkyl" refers to a straight or branched chain hydrocarbon that is fully saturated. For purposes of illustration, which should not be construed as limiting the scope of this invention, examples of alkyl include methyl, ethyl, propyl, isopropyl, butyl, pentyl, hexyl, and isomers thereof.

[0177] The term "alkenyl" refers to a hydrocarbon moiety containing 2 to 8 carbons, including straight-chain or branched hydrocarbons containing one or more double bonds. Non-limiting examples of alkenyl are ethenyl, propenyl, and butenyl.

[0178] The term "amorphous," when applied to a chemical compound, refers to a state in which the material lacks long-range order at the molecular level and may exhibit the physical properties of a solid or a liquid, depending on temperature. Typically, such materials do not produce distinctive X-ray diffraction patterns and exhibit the properties of a solid, but are more formally described as a liquid. Upon heating, a change from solid to liquid properties occurs, which is typically characterized by a second-order change of state (a "glass transition").

[0179] The term "anhydrous" when applied to a compound refers to a solid form of the compound that does not contain structural water within the crystal lattice.

[0180] The abbreviation "AP" refers to abdominal pain score. Unless otherwise specified, AP measurements discussed herein are unweighted 7-day averages of daily AP scores. AP measurements are calculated by averaging the daily AP scores used in calculating the CDAI (discussed below) without applying a weighting factor.

[0181] The term "aryl" refers to a monocyclic, bicyclic, or tricyclic aromatic hydrocarbon radical. Examples include phenyl, naphthyl, biphenyl, and 1,2,3,4-tetrahydronaphthyl.

[0182] As used herein, "AUC 24 The term "area under the plasma concentration-time curve" refers to the area under the plasma concentration-time curve from time 0 to 24 hours after administration of the reference drug according to a single dose.

[0183] The term "baseline" refers to the day of first administration of a JAK1 inhibitor, also referred to herein as "day 1" or "week 0."

[0184] The abbreviation "BID" stands for twice a day.

[0185] The abbreviation "BL" stands for baseline.

[0186] As used herein, "C 12 " is the plasma concentration of the reference drug observed 12 hours after administration of a single dose or the indicated number of doses of the reference drug.

[0187] As used herein, "C 24 " is the plasma concentration of the reference drug observed 24 hours after administration of a single dose or the indicated number of doses of the reference drug.

[0188] "C ave The term "mean plasma concentration of drug at steady state during the dosing interval (multiple doses)."

[0189] The abbreviation "Cbz" refers to carboxybenzyl.

[0190] The abbreviation "CDI" refers to carbonyldiimidazole.

[0191] The abbreviation "CI" stands for confidence interval.

[0192] The abbreviation "CDAI" stands for Crohn's Disease Activity Index.

[0193] The term "clinical remission," when used in connection with Crohn's disease, means an average daily number of liquid / very loose stools ≦2.8 and not exceeding baseline, and an average daily number of abdominal pains ≦1.0 and not exceeding baseline. When used in connection with clinical remission of Crohn's disease, the phrase "not exceeding baseline" means that the average daily SF or average daily AP score is not higher than the baseline (i.e., pre-treatment) average daily SF score or average daily AP score, respectively.

[0194] The term "clinical remission," when used in connection with ulcerative colitis, means a stool frequency (SF) subscore of ≦1, a rectal bleeding subscore (RBS) of 0, and an endoscopic subscore of ≦0. The SF subscore, rectal bleeding subscore, and endoscopic subscore refer to subscores used in the Mayo scoring system for assessment of ulcerative colitis activity. This term is also referred to as "clinical remission with an adapted Mayo score."

[0195] The term "clinical response", when used in connection with Crohn's disease, is defined as a reduction of at least 30% from BL (i.e., a reduction from BL of ≥ 30%) in the average daily SF score for liquid / very loose stools and / or an average daily AP not exceeding BL and / or a "clinical response" is defined as a reduction of at least 30% from BL (i.e., a reduction from BL of ≥ 30%) in the average daily AP score and an average daily SF score for liquid / very loose stools not exceeding BL (i.e., pre-treatment).

[0196] The term "clinical response" when used in relation to ulcerative colitis is defined as an adapted Mayo score of ≥ 2 points from baseline and a reduction of ≥ 30% from baseline, with a reduction of RBS ≥ 1 or an absolute RBS ≤ 1.

[0197] The term "enhanced clinical response," when used in relation to Crohn's disease, is defined as a reduction in mean daily SF of ≥ 60% and / or a reduction in mean daily AP of ≥ 35%, and both not exceeding baseline, and / or clinical remission.

[0198] Unless otherwise required by context, the terms "comprise," "comprises," and "comprising" are used with the express understanding that these terms are to be interpreted inclusively rather than exclusively, and that the applicant intends each of these terms to be so interpreted in interpreting this application, including the claims that follow.

[0199] "C max " refers to the T, expressed herein as ng / mL, resulting from oral ingestion of a dosage form or pharmaceutical composition, such as the dosage forms and compositions of the present disclosure, in a single dose or multiple doses indicated. max Unless specifically indicated, C max refers to the overall maximum concentration observed.

[0200] "C min The term "minimum plasma concentration of a drug" refers to the minimum plasma concentration of a drug.

[0201] The term "corticosteroid-naive" refers to patients who were taking corticosteroids at the time of the first induction dose of upadacitinib but have completely discontinued corticosteroid use.

[0202] "C p The term " refers to the plasma concentration of a drug at any time t.

[0203] The term "crystalline," when applied to a chemical compound, refers to a solid phase in which the material has a regular, ordered internal structure at the molecular level and produces a distinctive X-ray diffraction pattern with defined peaks. Such materials, when heated sufficiently, also exhibit the properties of a liquid, but the change from solid to liquid is typically characterized by a first-order phase change (a "melting point").

[0204] The term "crystallization" as used throughout this application can refer to crystallization and / or recrystallization depending on the circumstances applicable with respect to the preparation of the compound.

[0205] The abbreviation "CV%" refers to the coefficient of variation expressed as a percentage. CV% is calculated according to the following equation: CV% = (SD / x) x 100, where x is the mean and SD is the standard deviation.

[0206] A "disorder," as used herein, is any condition that can benefit from treatment with a JAK1 inhibitor as described herein, including chronic and acute disorders or diseases, including pathological conditions that predispose a mammal to the disorder.

[0207] The term "endoscopic healing" refers to an SES-CD ulcerated surface subscore of 0 in patients who had an SES-CD ulcerated surface subscore of ≧1 at baseline.

[0208] The term "endoscopic improvement" (also known as "50% endoscopic response"), when used in connection with Crohn's disease, means a >50% reduction from baseline in SES-CD (or for patients who had an SES-CD of 4 at baseline in the derivation study, a reduction of at least 2 points from baseline).

[0209] The term "endoscopic improvement," when used in connection with ulcerative colitis, means an endoscopic subscore of ≦1 at week 8 during the induction phase and an endoscopic subscore of 0 at week 8 during the maintenance phase. Endoscopic subscore refers to the subscore used in the Mayo scoring system for assessment of ulcerative colitis activity.

[0210] The term "endoscopic remission", when used in relation to Crohn's disease, unless otherwise specified, means an SES-CD ≦4 (≦2 for patients with isolated ileal CD) and at least a 2-point reduction in the SES-CD for BL and no subscores >1 in any individual variable used to calculate the SES-CD.

[0211] "The term endoscopic remission (as defined by the International Inflammatory Bowel Disease (IOIBD)) when used in relation to Crohn's disease means an SDS ≤ 2.

[0212] The term "endoscopic remission," when used in connection with ulcerative colitis, means an endoscopic subscore of 0. Endoscopic subscore refers to the endoscopic subscore used in the Mayo scoring system for assessment of ulcerative colitis activity.

[0213] The term "endoscopic response" when used in relation to Crohn's disease means at least a 50% reduction from BL in SES-CD score.

[0214] The abbreviation "EtOAc" refers to ethyl acetate.

[0215] The abbreviation "EtOH" refers to ethanol.

[0216] The term "Geboes score" refers to a histological score based on the measurement of fecal calprotectin and high-sensitivity C-reactive protein.

[0217] The term "histological improvement" when used in connection with ulcerative colitis means a decrease from baseline in Geboes score.

[0218] The abbreviation "HDL" refers to high density lipoprotein.

[0219] The abbreviation "Hgb" refers to hemoglobin.

[0220] The abbreviation "HOAc" refers to acetic acid.

[0221] The abbreviation "HPMC" refers to hydroxypropyl methylcellulose.

[0222] As used herein, the term "induction" or "induced," when used in connection with a specific therapeutic effect, means that a therapeutic effect has been achieved. Typically, a therapeutic effect is induced in a patient already suffering from a disease state, such as in a patient with moderately to severely active Crohn's disease or moderately to severely active ulcerative colitis. For example, in one embodiment, induction of a specific therapeutic effect, when used in connection with Crohn's disease, means that the patient transitions from a state in which the patient has 1) an average daily stool frequency score of liquid / very loose stools of ≥ 2.5 or an average daily abdominal pain frequency score of ≥ 2, 2) a CDAI of ≥ 220 and ≤ 450, or 3) a Simplified Endoscopy Score for Crohn's Disease (SES-CD) of ≥ 6 (or ≥ 4 for subjects with disease limited to the ileum), to a state in which the patient achieves the parameters for the specific therapeutic effect (e.g., endoscopic remission, clinical remission, endoscopic response, clinical response).

[0223] The abbreviation "IPAc" refers to isopropyl acetate.

[0224] The abbreviation "IR" means immediate release, unless otherwise specified.

[0225] As used herein, the term "JAK1 inhibitor" or "upadacitinib" refers to the compound (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

[0226] The abbreviation "LDL" refers to low-density lipoprotein.

[0227] The abbreviation "LOCF" refers to the last observation carried forward method.

[0228] The abbreviation "Mayo" refers to the Mayo scoring system for the assessment of ulcerative colitis activity.

[0229] The term "moderate to severe active Crohn's disease" is defined as an average daily number of very loose or liquid / loose stools ≥ 4, and / or an average daily abdominal pain score ≥ 2.0, and evidence of mucosal inflammation, with a Simplified Endoscopic Score for CD (SES-CD) ≥ 6 (≥ 4 for patients with isolated ileal disease), unless otherwise specified (excluding the presence of restricting factors).

[0230] The term "moderate to severe active ulcerative colitis" is defined as having a matched Mayo score of 5 to 9 with an endoscopic subscore of 2 or 3, unless otherwise specified.

[0231] The term "modified clinical remission," when used in connection with Crohn's disease, is defined as a mean daily liquid / very loose stool SF score of ≦2.8 and no greater than BL, and a mean daily AP score of ≦1.0 and no greater than BL. When used in connection with clinical remission, the phrase "not exceeding baseline" means that the mean daily liquid / very loose stool SF score or mean daily AP score is no higher than the baseline (i.e., pre-treatment) mean daily liquid / very loose stool SF score or mean daily AP score, respectively.

[0232] The abbreviation "MR" stands for modified release.

[0233] The abbreviation "MTX" refers to methotrexate.

[0234] The terms "patient" or "subject," as used interchangeably herein, refer to a human patient or subject.

[0235] The term "NK cells" refers to natural killer cells.

[0236] The abbreviation "NRI" stands for Non-Responder Imputation Method.

[0237] The abbreviation "PBO" stands for placebo.

[0238] The abbreviation "Pd / C" refers to palladium on carbon.

[0239] The abbreviation "Pd(OH2) / C" refers to palladium hydroxide on carbon.

[0240] The term "pharmaceutically acceptable" (as in reference to a "pharmaceutically acceptable salt" or a "pharmaceutically acceptable diluent") refers to a material that is compatible with administration to a human subject, e.g., the material does not cause undesired biological effects. Examples of pharmaceutically acceptable salts are described in "Handbook of Pharmaceutical Salts: Properties, Selection, and Use" by Stahl and Wermuth (Wiley-VCH, Weinheim, Germany, 2002). Examples of pharmaceutically acceptable excipients are described in "Handbook of Pharmaceutical Excipients" edited by Rowe et al. (Pharmaceutical Press, 7th ed., 2012).

[0241] The abbreviation "pTsOH" refers to p-toluenesulfonic acid.

[0242] The abbreviation "PVA" refers to polyvinyl acetate.

[0243] The abbreviation "PXRD" stands for powder X-ray diffraction.

[0244] The abbreviation "QD" stands for once daily.

[0245] The abbreviation "RBC" stands for red blood cells.

[0246] The abbreviation "RBS" stands for rectal bleeding subscore, which refers to a subscore used in the Mayo scoring system for assessment of ulcerative colitis activity.

[0247] The term "resistant patient" refers to a patient with moderate to severe active Crohn's disease who has had Crohn's disease for more than 10 years and who has failed several treatments, including biological treatments.

[0248] The term "remission," when used in connection with Crohn's disease, is defined as both endoscopic and clinical remission.

[0249] The term "response" when used in connection with Crohn's disease is defined as both an endoscopic response and a clinical response.

[0250] The abbreviation "SC" stands for subcutaneous.

[0251] The abbreviation "(S)-Segphos Ru(OAc)2" refers to diacetato[(S)-(-)5,5'-bis(diphenylphosphino)-4,4'-bi-1,3-benzodioxole]ruthenium(II).

[0252] The term "SES-CD" refers to the Simplified Endoscopic Score for Crohn's Disease, calculated using the parameters listed in Table 2 below.

[0253] The abbreviation "SF" refers to stool frequency. Unless otherwise specified, the SF measure discussed herein, when used in connection with Crohn's disease, is the 7-day unweighted average of the daily liquid / very loose stool SF scores. The SF measure is calculated by averaging the daily liquid / very loose stool SF scores used in calculating the CDAI (discussed below) without applying a weighting factor. Unless otherwise specified, the SF measure discussed herein, when used in connection with ulcerative colitis, refers to the stool frequency subscore used in the Mayo scoring system for assessing ulcerative colitis activity.

[0254] The term "therapeutically effective amount" is used to refer to an amount of an active agent that reduces or ameliorates one or more symptoms of the disorder being treated. In another embodiment, a therapeutically effective amount refers to a target serum concentration shown to be effective, for example, in slowing the progression of the disease. Efficacy can be measured in conventional manner depending on the condition being treated.

[0255] The abbreviation "6-TGN" refers to 6-thioguanine (thioguanine) nucleotide.

[0256] The abbreviation "THF" refers to tetrahydrofuran.

[0257] As used herein, "T max The term "time to peak plasma concentration of the reference drug after oral ingestion of a single dose or multiple indicated doses of the reference drug."

[0258] The terms "treating," "treatment," and "therapy," as used herein, are meant to include therapeutic as well as prophylactic or preventative measures for a disease or disorder that produce any clinically desirable or beneficial effect, including, but not limited to, the alleviation or alleviation of, regression, slowing, or halting of progression of, one or more symptoms of the disease or disorder. Thus, for example, the term treatment includes administering an agent before or after the onset of symptoms of the disease or disorder, thereby preventing or eliminating one or more signs of the disease or disorder. As another example, the term includes administering an agent after clinical manifestation of a disease to combat symptoms of the disease. Furthermore, post-onset and post-clinical administration of agents has been developed, where the administration affects clinical parameters of the disease or disorder, such as the degree of tissue damage or the amount or extent of metastasis, and as used herein, includes "treatment" or "therapy," regardless of whether the treatment alleviates the disease. Furthermore, so long as the compositions of the present disclosure, alone or in combination with another therapeutic agent, reduce or ameliorate at least one symptom of the disorder being treated compared to the symptoms in the absence of the JAK1 inhibitor composition, the result should be considered an effective treatment of the underlying disorder, regardless of whether all of the symptoms of the disorder are alleviated.

[0259] The abbreviation "TNF" stands for tumor necrosis factor.

[0260] As used herein, "t 1 / 2 The term "" refers to the terminal half-life of a reference drug after oral ingestion of a single dose or multiple indicated doses of the reference drug.

[0261] The abbreviation "UC" refers to ulcerative colitis.

[0262] The abbreviation "w / w" refers to weight / weight.

[0263] II. JAK1-Related Disorders and JAK1 Inhibitors In one aspect, the present disclosure provides methods for treating and / or inducing clinical remission, endoscopic improvement, and / or endoscopic remission of Crohn's disease. In another aspect, the present disclosure provides methods for treating and / or inducing clinical remission of ulcerative colitis. In one aspect, the method comprises administering a JAK1 inhibitor to a patient.

[0264] Targeting the JAK (Janus-activated kinase) signaling pathway for autoimmune diseases such as rheumatoid arthritis (RA) and CD is well supported by the involvement of various proinflammatory cytokines that signal through the JAK pathway in the pathogenesis of these immune-related disorders. Activation of JAK signaling triggers the expression of survival factors, cytokines, chemokines, and other molecules that facilitate white blood cell trafficking and cell proliferation, contributing to inflammatory and autoimmune disorders.

[0265] Although the pathogenesis of CD is not fully understood, an imbalance between anti- and pro-inflammatory cytokines in the mucosal immune system is thought to play an important role in CD. Cells derived from the innate mucosal immune system, i.e., TNF-1 or TNF-17, are overactivated and secrete various pro-inflammatory cytokines, such as interferon (IFN)-g, tumor necrosis factor (TNF-α), interleukins IL-6, IL-1b, IL-12, and IL-23. These cytokines signal via the JAK pathway.

[0266] JAKs include four family members: JAK1, 2, 3, and tyrosine kinase 2 (Tyk2). These cytoplasmic tyrosine kinases transduce cytokine-mediated signals and associate with membrane cytokine receptors such as the common gamma chain (CGC) receptor and glycoprotein 130 (gp130) transmembrane protein.

[0267] JAK3 and JAK1 are components of the CGC cytokine receptor complex, and blocking either of them inhibits signaling by the proinflammatory cytokines IL-2, -4, -7, -9, -15, and -21. Cytokines such as IL-6 bind to gp130 and transmit their signals primarily through JAK1. Given that the expression of IL-6 receptor and soluble IL-6 receptor is elevated in patients with active CD, targeting the IL-6 receptor (IL-6R) is a promising approach. Furthermore, a proof-of-concept study using tocilizumab, a humanized monoclonal antibody against IL-6R, in patients with active CD showed promising clinical responses. Therefore, inhibition of JAK1 is predicted to attenuate signaling of IL-6 and other proinflammatory cytokines (i.e., IFN-γ) involved in the pathogenesis of CD.

[0268] Thus, in one aspect, the present disclosure provides compounds useful in the treatment of Crohn's disease and ulcerative colitis. In one aspect, the JAK1 inhibitor used in the methods of the present disclosure is the compound (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide (C 17 H 19 FNO), or a pharmaceutically acceptable salt or solid form thereof. Also, the compound (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide, referred to herein as "upadacitinib," has the structure shown below.

[0269] [ka]

[0270] "Pharmaceutically acceptable salts" refers to salts which retain the biological effectiveness and properties of the free base and which are obtained by reaction with inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid, or organic acids such as sulfonic acids, carboxylic acids, organophosphoric acids, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, citric acid, fumaric acid, maleic acid, succinic acid, benzoic acid, salicylic acid, lactic acid, tartaric acids such as monomalic acid, monooxalic acid, monotartaric acid (e.g., (+) or (-)-tartaric acid, or mixtures thereof), amino acids (e.g., (+) or (-)-amino acids, or mixtures thereof), etc. These salts can be prepared by methods known to those skilled in the art.

[0271] III. Methods of Treating Crohn's Disease In one aspect, the present disclosure is directed to a method for treating Crohn's disease. In one aspect, the present disclosure provides a method for treating Crohn's disease, particularly a method comprising administering a JAK1 inhibitor to a patient in a specific amount and / or at a specific interval. In one aspect, the JAK1 inhibitor is upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0272] In one aspect, the disclosure provides a JAK1 inhibitor for use in treating Crohn's disease by administration in a certain amount and / or at certain intervals, as described herein. In one aspect, the JAK1 inhibitor is upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0273] In one aspect, the disclosure provides use of a JAK1 inhibitor for preparing a medicament for the treatment of Crohn's disease by administering in a specific amount and / or at a specific interval, as described herein. In one aspect, the JAK1 inhibitor is upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0274] In one aspect, the present disclosure is directed to methods for inducing clinical and / or endoscopic remission of Crohn's disease. In one aspect, the present disclosure provides methods for inducing clinical and / or endoscopic remission of Crohn's disease, particularly methods comprising administering a JAK1 inhibitor to a patient in a specific amount and / or at specific intervals. In one aspect, the JAK1 inhibitor is upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0275] In one aspect, the present disclosure provides a JAK1 inhibitor for use in inducing clinical and / or endoscopic remission of Crohn's disease by administration in a certain amount and / or at certain intervals, as described herein. In one aspect, the JAK1 inhibitor is upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0276] In one aspect, the disclosure provides use of a JAK1 inhibitor for the preparation of a medicament for inducing clinical and / or endoscopic remission of Crohn's disease by administration in a specific amount and / or at a specific interval, as described herein. In one aspect, the JAK1 inhibitor is upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0277] In one aspect, the present disclosure is directed to methods for inducing clinical remission and / or endoscopic improvement in Crohn's disease, particularly methods comprising administering to a patient a JAK1 inhibitor in a specific amount and / or at specific intervals. In one aspect, the JAK1 inhibitor is upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0278] In one aspect, the disclosure provides a JAK1 inhibitor for use in inducing clinical remission and / or endoscopic improvement in Crohn's disease by administration in a certain amount and / or at certain intervals, as described herein. In one aspect, the JAK1 inhibitor is upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0279] In one aspect, the disclosure provides use of a JAK1 inhibitor for the preparation of a medicament for inducing clinical remission and / or endoscopic improvement in Crohn's disease by administration in a specific amount and / or at a specific interval, as described herein. In one aspect, the JAK1 inhibitor is upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0280] In one particular aspect, the disease is moderate to severe active Crohn's disease. In one aspect, in the context of the present disclosure, the patient is not receiving or has already been treated with an immunosuppressant (e.g., methotrexate), an aminosalicylate, a corticosteroid, and / or a biologic agent (e.g., vedolizumab, ustekinumab, natalizumab, etc.). In one aspect, the patient is not receiving or has already been treated with an anti-TNF therapy (e.g., infliximab, adalimumab, certolizumab pegol, golimumab, etc.). In one aspect, in the context of the method of the present disclosure, the patient is already treated with one, two, three or more TNF antagonists (also referred to herein as anti-TNF agents). In one embodiment, the patient is a patient who has had an inadequate response, lost response, or was intolerant to a TNF antagonist. In one aspect, in the context of the method of the present disclosure, the patient has already been treated with one, two, three or more biologic agents. In one embodiment, the patient is a patient who has had an inadequate response, lost response, or was intolerant to the biologic agents. In one embodiment, the patient is a patient who has had an inadequate response, lost response, or was intolerant to TNF antagonists, aminosalicylates, corticosteroids, immunosuppressants, and / or biologic agents. In one embodiment, the patient is a resistant patient with moderate to severe active Crohn's disease. In one embodiment, the patient is either not receiving or has discontinued use of corticosteroids prior to treatment with a JAK1 inhibitor.

[0281] Biologic agents for Crohn's disease 1) Demonstrated inadequate response, loss of response, recurrence of signs and symptoms, or intolerance to any biologic treatment, as defined below. At least one 6-week induction regimen of infliximab (≥ 5 mg / kg intravenously [IV] at weeks 0, 2, and 6), b. At least one 4-week induction regimen of adalimumab (one 160 mg subcutaneous (SC) dose at week 0 followed by one 80 mg SC dose at week 2 [or one 80 mg SC dose at week 0 followed by one 40 mg SC dose at week 2 (in countries where this dosing regimen is approved)]), c. At least one 4-week induction regimen of certolizumab pegol (400 mg SC at weeks 0, 2, and 4), d. At least one 6-week induction regimen of vedolizumab (300 mg IV at weeks 0, 2, and 6), e. At least one 12-week induction regimen of natalizumab (300 mg IV every 4 weeks), f. At least one 8-week induction regimen of ustekinumab (260 mg (<55 kg) or 390 mg (56-85 kg) or 520 mg (>86 kg) SC followed by 90 mg at week 8); or 2) recurrence of symptoms during maintenance treatment planned according to previous clinical benefit (withdrawal despite clinical benefit is not permitted); or 3) History of intolerance to at least one biologic agent (including but not limited to infusion reactions, demyelination, congestive heart failure (CHF), infection).

[0282] Disease severity for Crohn's disease can be measured using various indices, including the Crohn's Disease Activity Index (CDAI), the Simplified Endoscopic Score for CD (SES-CD), the average number of daily stools (SF) (patient-recorded) for liquid / very loose stools, and / or the average number of daily abdominal pain (AP) scores (patient-recorded). Unless otherwise specified, the SF and AP scores discussed herein refer to their respective unweighted means of the daily scores used in calculating the CDAI (discussed below). Measures for assessing health-related quality of life include the Inflammatory Bowel Disease Questionnaire (IBDQ). The IBDQ is a well-known, validated 32-item questionnaire that assesses a patient's inflammatory bowel disease symptoms, general health, and mood, and can be used as a tool to evaluate a patient's quality of life (Guyatt et al., Gastroenterology, 1989, 96:804-810). The IBDQ questionnaire is described in further detail below.

[0283] The CDAI is a composite score used to quantify symptoms in patients with Crohn's disease. In one embodiment, the index consists of eight factors summed after adjusting for predefined weighting coefficients (see Table 1 below). CDAI scores range from 0 to 600. An index value of 150 or less is associated with inactive disease, a value above 150 is associated with active disease, and a value above 450 is seen in very severe disease. In one embodiment, patients treated by the methods disclosed herein have a CDAI score of 220 to 450 before treatment, which may indicate moderate to severe active CD.

[0284] [Table 1]

[0285] The SES-CD is calculated using the following parameters, listed in Table 2:

[0286] [Table 2]

[0287] In one embodiment, the patient to be treated has moderately to severely active Crohn's disease, characterized by an SES-CD of 6 or greater (or for patients with disease limited to the ileum, an SES-CD of 4 or greater).

[0288] In one embodiment, the patient is one who has had an inadequate response, lost response, or been intolerant to conventional therapy (e.g., aminosalicylates, corticosteroids, immunosuppressants) or biologic agents. In one embodiment, the patient is one who has had an inadequate response, lost response, or been intolerant to TNF antagonists. Examples of such anti-TNF agents include infliximab, adalimumab, and certolizumab pegol. The criteria for determining whether a patient has had an inadequate response or experienced intolerance to prior treatment with an anti-TNF agent are defined as follows:

[0289] 1) Signs and symptoms of persistently active disease despite a history of at least one 4-week induction regimen of one of the following medications: Infliximab: 5 mg / kg IV, 2 doses at least 2 weeks apart Adalimumab: One subcutaneous dose of 160 mg followed by one subcutaneous dose of 80 mg (or one subcutaneous dose of 80 mg followed by one subcutaneous dose of 40 mg) at least 2 weeks apart, Certolizumab pegol: Two subcutaneous doses of 400 mg, separated by at least two doses; or 2) recurrence of symptoms during maintenance treatment planned according to previous clinical benefit (withdrawal despite clinical benefit is not permitted); or 2) recurrence of symptoms during maintenance treatment planned according to previous clinical benefit (withdrawal despite clinical benefit is not permitted); or 3) History of intolerance to at least one TNF antagonist (including but not limited to infusion reactions, demyelination, congestive heart failure, and infection).

[0290] In one embodiment, the patient is one who has been previously treated or is currently undergoing treatment with an aminosalicylate, an immunosuppressant, a corticosteroid and / or a biologic agent.

[0291] In one aspect, the CDAI or any of the assessments described in the Examples herein below is used to assess the efficacy of upadacitinib in treating Crohn's disease, e.g., moderately to severely active Crohn's disease.

[0292] In one embodiment of the present disclosure, treatment of a patient, or induction of clinical and / or endoscopic remission in a patient, or induction of clinical remission and / or endoscopic improvement in a patient, includes an induction phase and a maintenance phase. In the induction phase, for example, one or more doses of a JAK1 inhibitor, referred to herein as induction doses, are administered to the patient, for example, orally. In the maintenance phase, for example, a first dose of a JAK1 inhibitor, referred to herein as a maintenance dose, is administered to the patient, followed by at least one additional dose of a JAK1 inhibitor, also referred to herein as a maintenance dose. The maintenance dose is administered, for example, orally. The JAK1 inhibitor can be, for example, upadacitinib or a pharmaceutically acceptable salt or solid form thereof. Examples of induction and maintenance phases are described herein.

[0293] In one aspect, a particular therapeutic outcome, e.g., clinical remission, endoscopic remission, or both clinical remission and endoscopic remission (referred to herein as "remission"), is achieved by the patient during or at the end of the induction phase. In one aspect, the patient achieves clinical remission during or by the end of the induction phase. In one aspect, the patient achieves endoscopic remission during or by the end of the induction phase.

[0294] In another aspect, a particular therapeutic outcome, e.g., clinical remission, endoscopic improvement, or both clinical remission and endoscopic improvement, is achieved by the patient during or at the end of the induction phase. In one aspect, the patient achieves clinical remission during or by the end of the induction phase. In one aspect, the patient achieves endoscopic improvement during or by the end of the induction phase.

[0295] In one embodiment, the induction phase lasts for up to 16 weeks (e.g., up to 16 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof). Thus, in one embodiment, the induction phase is 16 weeks. In another embodiment, the induction phase optionally lasts for less than 16 weeks, e.g., 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 weeks. In one aspect, the patient achieves endoscopic remission within 12 weeks or within 16 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one aspect, the patient achieves clinical remission within 16 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one aspect, the patient achieves endoscopic improvement within 12 weeks or within 16 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the patient achieves clinical remission within 12 weeks or within 16 weeks of starting administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0296] In one embodiment, the patient achieves clinical remission within two weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the patient achieves clinical remission within four weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0297] In one embodiment, a patient achieves both 1) a mean daily SF score for liquid / very loose stools of ≦1.5 and no worse than BL, and 2) a mean daily AP score of ≦1.0 and no worse than baseline within 2 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. When used in the context of clinical remission, the phrase "no worse than baseline" means that the mean daily SF score for liquid / very loose stools or the mean daily AP score, respectively, is no higher than the baseline (i.e., pre-treatment) mean daily SF score for liquid / very loose stools or the mean daily AP score.

[0298] In one embodiment, a patient achieves both 1) a mean daily SF score for liquid / very loose stools of ≦1.5 and no worse than BL, and 2) a mean daily AP score of ≦1.0 and no worse than baseline within 4 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. When used in the context of clinical remission, the phrase "no worse than baseline" means that the mean daily SF score for liquid / very loose stools or the mean daily AP score, respectively, is no higher than the baseline (i.e., pre-treatment) mean daily SF score for liquid / very loose stools or the mean daily AP score.

[0299] In one embodiment, the patient achieves endoscopic remission and / or endoscopic improvement within 2 weeks after initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the patient achieves endoscopic remission and / or endoscopic improvement within 12 weeks after initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0300] In one embodiment, the patient achieves corticosteroid-free remission within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0301] In some embodiments, during or by the end of the induction phase (e.g., including 2 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks, or 16 weeks, continuing up to 16 weeks), the patient achieves at least one therapeutic outcome selected from the group consisting of: 1) A CDAI of less than 150 within 16 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof; 2) A CDAI of less than 150 within 12 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof; 3) CDAI of less than 150 within 4 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof; 4) A 70-point or greater reduction from baseline in CDAI within 16 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 5) A 70-point or greater reduction from baseline in CDAI within 12 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 6) A 70-point or greater reduction from baseline in CDAI within 4 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 7) Clinical remission within 12 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 8) Clinical remission within 4 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 9) Remission within 16 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof (i.e., both endoscopic remission within 12 weeks or 16 weeks and clinical remission within 16 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof), 10) Remission within 12 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof (i.e., both endoscopic remission within 12 weeks and clinical remission within 12 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof), 11) Remission within 4 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof (i.e., both endoscopic remission within 4 weeks and clinical remission within 4 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof), 12) Response within 16 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof (i.e., both endoscopic response within 12 weeks or 16 weeks and clinical response within 16 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof), 13) Response within 12 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof (i.e., both endoscopic response within 12 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof and clinical response within 12 weeks), 14) Response within 4 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof (i.e., both endoscopic response within 4 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof and clinical response within 4 weeks), 15) Endoscopic response within 12 weeks or 16 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 16) Endoscopic response within 4 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 17) Clinical response within 16 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 18) Clinical response within 12 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 19) Clinical response within 4 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 20) Clinical response within 2 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 21) Change from baseline in fecal calprotectin levels within 16 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, 22) Change from baseline in fecal calprotectin levels within 12 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, 23) Change from baseline in fecal calprotectin levels within 4 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, 24) Change from baseline in hs-CRP (high sensitivity C-reactive protein) within 16 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, 25) Change from baseline in hs-CRP (high sensitivity C-reactive protein) within 12 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, 26) Change from baseline in hs-CRP (high sensitivity C-reactive protein) within 8 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, 27) Change from baseline in hs-CRP (high-sensitivity C-reactive protein) within 4 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, 28) Change from baseline in hs-CRP (high-sensitivity C-reactive protein) within 2 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, 29) Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) score within 16 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, 30) Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) score within 12 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, 31) Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) score within 8 weeks after initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, 32) Controlled clinical remission within 4 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; 33) Enhanced clinical response within 8 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; and combinations thereof, 34) Steroid-free endoscopic improvement within 4 weeks after administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 35) Steroid-free endoscopic improvement within 8 weeks after administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; 36) Steroid-free endoscopic improvement within 16 weeks after administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; 37) A steroid-free endoscopic response within 4 weeks of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 38) A steroid-free endoscopic response within 8 weeks of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 39) A steroid-free endoscopic response within 16 weeks of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 40) Steroid-free endoscopic remission within 4 weeks after administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; 41) Steroid-free endoscopic remission within 8 weeks after administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; 42) Steroid-free endoscopic remission within 16 weeks after administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0302] In some embodiments, the patient achieves either clinical remission within 16 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, or endoscopic remission within 12 weeks or within 16 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, and also achieves any combination of additional therapeutic outcomes selected from the group consisting of treatment outcomes 1), 2), 3), 4), 5), 6), 7), 8), 9), 10), 11), 12), 13), 14), 15), 16), 17), 18), 19), 20), 21), 22), 23), 24), 25), 26), 27), 28), 29), and combinations thereof. In one such embodiment, the induction phase is 16 weeks.

[0303] In one embodiment, the induction phase is 12 weeks long and the patient achieves either clinical remission within 12 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, or endoscopic remission within 12 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, and any combination of additional therapeutic outcomes selected from the group consisting of therapeutic outcomes 2), 3), 5), 6), 7), 8), 10), 11), 13), 14), 15), 16), 18), 19), 20), 22), 23), 25), 26), 28), 29), and combinations thereof, wherein the therapeutic outcome is achieved within 12 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0304] In one embodiment, the induction phase is 4 weeks long and the patient achieves either clinical remission within 4 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, or endoscopic remission within 4 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, and any combination of additional therapeutic outcomes selected from the group consisting of therapeutic outcomes 3), 6), 8), 11), 14), 16), 19), 20), 23), 26), 29), and combinations thereof, wherein the therapeutic outcome is achieved within 4 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0305] In one embodiment, the patient achieves clinical remission within 12 weeks or 16 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof and / or achieves endoscopic improvement within 12 weeks or 16 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, and any combination of additional treatment outcomes selected from the group consisting of treatment outcomes 1), 2), 3), 4), 5), 6), 7), 8), 9), 10), 11), 12), 13), 14), 15), 16), 17), 18), 19), 20), 21), 22), 23), 24), 25), 26), 27), 28), 29), and combinations thereof. In one such embodiment, the induction phase is 16 weeks.

[0306] In one embodiment, the induction phase is 12 weeks long, and the patient achieves clinical remission within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, and / or achieves endoscopic improvement within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, and any combination of additional therapeutic outcomes selected from the group consisting of therapeutic outcomes 2), 3), 5), 6), 7), 8), 10), 11), 13), 14), 15), 16), 18), 19), 20), 22), 23), 25), 26), 28), 29), and combinations thereof, wherein the therapeutic outcome is achieved within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0307] In one embodiment, the induction phase is 16 weeks long and the patient achieves clinical remission within 16 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof and / or achieves endoscopic improvement within 16 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, and any combination of additional therapeutic outcomes selected from the group consisting of therapeutic outcomes 1), 2), 3), 4), 5), 6), 7), 8), 9), 10), 11), 12), 13), 14), 15), 16), 17), 18), 19), 20), 21), 22), 23), 24), 25), 26), 27), 28), 29), and combinations thereof, wherein the therapeutic outcome is achieved within 16 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0308] In one embodiment, the induction phase is 4 weeks long, and the patient achieves clinical remission within 4 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, and / or achieves endoscopic improvement within 4 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, and any combination of additional therapeutic outcomes selected from the group consisting of therapeutic outcomes 3), 6), 8), 11), 14), 16), 19), 20), 23), 26), 29), and combinations thereof, wherein the therapeutic outcome is achieved within 4 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0309] In one embodiment, the patient achieves clinical remission within 4 weeks, 12 weeks, or 16 weeks of initiating upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, and / or achieves endoscopic improvement within 4 weeks, 12 weeks, or 16 weeks of initiating upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, and further achieves a CDAI of less than 150 within 16 weeks of initiating upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; a CDAI of less than 150 within 12 weeks of initiating upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; a CDAI of less than 150 within 4 weeks of initiating upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; and achieving an additional therapeutic outcome selected from the group consisting of: endoscopic remission within 16 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; endoscopic remission within 12 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; endoscopic remission within 4 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; a clinical response within 16 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; a clinical response within 12 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; a clinical response within 4 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; a clinical response within 2 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; and combinations thereof. In one such embodiment, the induction phase is 16 weeks long and the additional treatment outcome is selected from the group consisting of: a CDAI of less than 150 within 16 weeks, or within 12 weeks, or within 4 weeks, or within 2 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; an endoscopic remission within 16 weeks, or within 12 weeks, or within 4 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; a clinical response within 16 weeks, or within 12 weeks, or within 4 weeks, or within 2 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; and combinations thereof.In one such embodiment, the induction phase is 12 weeks long and the additional treatment outcome is selected from the group consisting of: a CDAI of less than 150 within 12 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; an endoscopic remission within 12 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; a clinical response within 12 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; and combinations thereof.

[0310] In one embodiment, an additional treatment outcome may further be clinical remission within 16 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, wherein the patient has a mean daily SF score of liquid / very loose stools of 2.5 or greater and a mean daily AP score of 2.0 or greater at baseline. In one embodiment, if the patient was taking corticosteroids at baseline but discontinued corticosteroid use during treatment with a JAK1 inhibitor, the additional treatment outcomes may be selected from the group consisting of a CDAI score of less than 150 within 16 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; endoscopic remission within 12 weeks or within 16 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, and clinical remission within 16 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; clinical remission within 16 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; and endoscopic remission within 12 weeks or within 16 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; and combinations thereof. In one embodiment, if the patient has isolated ileal Crohn's disease, an additional treatment outcome may further be remission within 16 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one aspect, the patient achieves a CDAI score of less than 150 during or by the end of the induction phase.

[0311] In one aspect, the patient may achieve an additional treatment outcome selected from the group consisting of clinical remission (i.e., mean daily SF score ≦2.8 and not exceeding baseline, and mean daily AP score ≦1.0 and not exceeding baseline) within 16 weeks after initiation of administration of padacitinib, or a pharmaceutically acceptable salt or solid form thereof; endoscopic improvement (i.e., an SES-CD score that is greater than 50% reduction from baseline, or a reduction of at least a 2-point SES-CD score from baseline, or endoscopic remission) within 4 weeks, 6 weeks, 12 weeks, or 16 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; and combinations thereof.

[0312] In one aspect, the patient may achieve an additional treatment outcome selected from the group consisting of a reduction in CDAI score of 70 or more from baseline and a reduction in CDAI score of 100 or more from baseline. In one embodiment, the induction phase is 16 weeks and the reduction in CDAI occurs within 16 weeks or within 12 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the induction phase is 12 weeks and the reduction in CDAI occurs within 12 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0313] In one particular embodiment, the induction phase is 16 weeks long, and patients achieve clinical remission within 16 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; endoscopic improvement (i.e., a greater than 50% reduction in SES-CD score from baseline, or at least a 2-point reduction in SES-CD score from baseline, or endoscopic remission) within 4 weeks, 6 weeks, 12 weeks, or 16 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, or a combination thereof. In another embodiment, the induction phase is 12 weeks long, and patients achieve clinical remission within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; endoscopic improvement within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; or a combination thereof.

[0314] In one embodiment, the patient is administered upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, for at least 52 weeks. The administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, may include an induction phase (e.g., an induction phase of up to 16 weeks) and an additional week (e.g., 36 weeks or more) of maintenance phase (discussed below). In other embodiments, the administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, may include a shorter induction phase (e.g., up to 2 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, up to 12 weeks, etc.) and a longer maintenance phase (e.g., a 12-week induction phase and a 40-week or more maintenance phase).In some such embodiments, the patient achieves remission within 52 weeks after initiation of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; endoscopic remission within 52 weeks after initiation of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; clinical remission within 52 weeks after initiation of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; Endoscopic improvement within 52 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; response within 52 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; endoscopic response within 52 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; clinical response within 52 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof At least one therapeutic outcome selected from the group consisting of: a CDAI of less than 150 within 52 weeks after initiation; a 70-point or greater reduction in CDAI from baseline within 52 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; a change in fecal calprotectin levels from baseline within 52 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; a change in hs-CRP from baseline within 52 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; a change in IBDQ score from baseline within 52 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; a change in extraintestinal symptoms (EIMS) from baseline within 52 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; and combinations thereof may be achieved.

[0315] In some embodiments, when a patient is administered upadacitinib or a pharmaceutically acceptable salt or solid form thereof for at least 52 weeks, and the patient was taking corticosteroids at baseline but discontinued corticosteroid use during treatment with a JAK1 inhibitor, the additional treatment outcome may be selected from the group consisting of: a CDAI of less than 150 within 52 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; remission within 52 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; clinical remission within 52 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; and endoscopic remission within 52 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; and combinations thereof. In one embodiment, if the patient has isolated ileal Crohn's disease, an additional treatment outcome may further be remission within 52 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0316] In one embodiment of the disclosed method, the patient is assessed during or at the end of the induction phase for a treatment outcome selected from the group consisting of clinical remission, endoscopic improvement, endoscopic remission, endoscopic response, clinical response, CDAI, mean daily SF score for liquid / very loose stools, mean daily AP score, fecal calprotectin level, hs-CRP, IBDQ score, and combinations thereof. In one embodiment of the disclosed method, the patient is assessed for clinical remission during or at the end of the induction phase. In one embodiment of the disclosed method, the patient is assessed for endoscopic improvement during or at the end of the induction phase. In one embodiment of the disclosed method, the patient is assessed for endoscopic remission during or at the end of the induction phase.

[0317] In one embodiment, the patient is administered at least 14 doses, or at least 28 doses, or at least 42 doses, or at least 70 doses, or at least 84 doses, or at least 112 doses, or at least 140 doses, or at least 168 doses, or at least 224 doses, or 70 doses, or 84 doses, or 112 doses, or 140 doses, or 168 doses, or 224 doses of upadacitinib or a pharmaceutically acceptable salt or solid form thereof during the induction phase.

[0318] In one aspect, certain therapeutic outcomes are maintained by the patient during the maintenance phase. The maintenance phase may be continued indefinitely. In one embodiment, the maintenance phase is at least 36 weeks, including at least 37 weeks, at least 38 weeks, at least 39 weeks, at least 40 weeks, at least 41 weeks, at least 42 weeks, at least 43 weeks, at least 44 weeks, at least 45 weeks, at least 46 weeks, at least 47 weeks, or at least 48 weeks. In one embodiment, the maintenance phase is at least 40 additional weeks. In one embodiment, the therapeutic outcome maintained by the patient during the maintenance phase is selected from the group consisting of clinical remission, endoscopic remission, and a combination thereof. In one embodiment, the therapeutic outcome maintained by the patient during the maintenance phase is selected from the group consisting of clinical response, endoscopic improvement, and a combination thereof. In one aspect, the patient maintains a CDAI score of less than 150 during the maintenance phase. In one aspect, the patient maintains an SES-CD that is greater than a 50% reduction from the patient's baseline SES-CD. In one embodiment, the patient maintains an SES-CD that is at least a 2-point reduction from the patient's baseline SES-CD. In one embodiment, the therapeutic outcome maintained by the patient during the maintenance phase is a clinical response. In one embodiment, the therapeutic outcome maintained by the patient during the maintenance phase is endoscopic remission.

[0319] In one embodiment of the disclosed method, the patient is evaluated for clinical remission during the maintenance phase. In one embodiment, the patient is evaluated for endoscopic improvement during the maintenance phase. In one embodiment of the disclosed method, the patient is evaluated for endoscopic remission during the maintenance phase.

[0320] In one embodiment, the disclosure provides a method for treating an inflammatory disease, in one aspect, for treating Crohn's disease, comprising: (a) administering to a patient a dose of a JAK1 inhibitor (e.g., upadacitinib or a pharmaceutically acceptable salt or solid form thereof) once daily (QD) at week 0 and thereafter for 16 weeks, wherein the dose is 45 mg QD. In one embodiment, the method further comprises: (b) administering to the patient an additional dose once daily thereafter for at least an additional 36 weeks, wherein the dose is 15 mg or 30 mg QD. In one embodiment, the dose is administered orally.

[0321] In one embodiment, at Week 12 (i.e., 12 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof), patients are assessed for clinical remission (mean daily SF score for liquid / very loose stools ≦2.8 and no worse than baseline, and mean daily AP score ≦1.0 and no worse than baseline) and / or endoscopic remission (SES-CD ≦4 (or SES-CD ≦2 for patients with isolated ileal CD) and at least a 2-point reduction in SES-CD for BL and no subscores >1 in any individual variable used to calculate the SES-CD). In one embodiment, at Week 16 (i.e., 16 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof), patients are assessed for clinical remission and / or endoscopic remission.

[0322] In one embodiment, at week 4 (i.e., 4 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof), patients are assessed for clinical remission (mean daily SF score for liquid / very loose stools ≦2.8 and no worse than baseline, and mean daily AP score ≦1.0 and no worse than baseline) and / or endoscopic remission (SES-CD ≦4 (or SES-CD ≦2 for patients with isolated ileal CD) and at least a 2-point reduction in SES-CD for BL and no subscores >1 in any individual variable used to calculate SES-CD).

[0323] In one embodiment, at week 16 (i.e., 16 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof), patients are assessed for remission, which is defined as, for example, achieving clinical remission (mean daily SF score for liquid / very loose stools ≦2.8 and no worse than baseline, and mean daily AP score ≦1.0 and no worse than baseline) and endoscopic remission (SES-CD ≦4 (or SES-CD ≦2 for patients with isolated ileal CD) and at least a 2-point reduction in SES-CD for BL and no subscores >1 in any individual variable used to calculate SES-CD).

[0324] In one embodiment, at week 12 (i.e., 12 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof), the patient is assessed for clinical remission and / or endoscopic improvement. In one embodiment, at week 16 (i.e., 16 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof), the patient is assessed for clinical remission and / or endoscopic improvement.

[0325] In one embodiment, at week 4 (i.e., four weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof), the patient is assessed for clinical remission and / or endoscopic improvement. In one embodiment, at week 2 (i.e., two weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof), the patient is assessed for clinical remission and / or endoscopic improvement.

[0326] In one embodiment, the disclosure provides a method for treating Crohn's disease, comprising: (a) administering a dose of a JAK1 inhibitor (e.g., upadacitinib or a pharmaceutically acceptable salt or solid form thereof) via oral route to a patient at week 0 and once daily thereafter, wherein the dose of the JAK1 inhibitor comprises 15 mg, 30 mg, or 45 mg QD, or any combination thereof.

[0327] In one embodiment, the disclosure provides a method for treating Crohn's disease, comprising administering 15 mg to 45 mg of a JAK1 inhibitor to a patient. In one embodiment, the disclosure provides a method for treating Crohn's disease, comprising orally administering 15 mg of a JAK1 inhibitor QD to a patient. In one embodiment, the disclosure provides a method for treating Crohn's disease, comprising orally administering 30 mg of a JAK1 inhibitor QD to a patient. In one embodiment, the disclosure provides a method for treating Crohn's disease, comprising orally administering 45 mg of a JAK1 inhibitor QD to a patient. In any such embodiment, the JAK1 inhibitor can be upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In any such embodiment, the JAK1 inhibitor can be in a once-daily modified-release formulation. In any such embodiment, the patient can have moderate to severe active Crohn's disease prior to treatment.

[0328] In one embodiment, administration of a JAK1 inhibitor according to the present disclosure is further described in the Examples herein below or in FIG.

[0329] In one embodiment, the disclosure provides a method for treating Crohn's disease, comprising: a) administering to a patient at least one induction dose of a JAK1 inhibitor (e.g., upadacitinib or a pharmaceutically acceptable salt or solid form thereof), wherein the induction dose comprises 45 mg of the JAK1 inhibitor. In one aspect, the induction dose is administered orally. In one aspect, the induction dose is administered QD. In one aspect, the induction dose is administered for 12 weeks. In one aspect, the induction dose is administered for 16 weeks. In one embodiment, the induction dose is administered for up to 16 weeks, including 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 weeks.

[0330] In one embodiment, the induction dose comprises 45 mg of a JAK1 inhibitor administered QD.

[0331] In one embodiment, the JAK1 inhibitor is upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0332] In one embodiment, the loading dose is in a once-daily modified release formulation.

[0333] In one embodiment, the method further comprises: b) administering to the patient a first maintenance dose of a JAK1 inhibitor (e.g., upadacitinib or a pharmaceutically acceptable salt or solid form thereof) after the final induction dose has been administered; and c) thereafter administering to the patient at least one additional maintenance dose once daily.

[0334] In one embodiment, the first maintenance dose comprises 15 mg to 30 mg of the JAK1 inhibitor. In one aspect, the first maintenance dose comprises 15 mg or 30 mg of the JAK1 inhibitor. In one aspect, the first maintenance dose is less than the induction dose. In one aspect, the first maintenance dose is administered QD. In one aspect, the first maintenance dose is 15 mg. In one aspect, the first maintenance dose is 30 mg. In one aspect, the first maintenance dose is administered orally. In one aspect, the first maintenance dose is a once-daily dose in a modified release formulation.

[0335] In one aspect, the at least one additional maintenance dose comprises 15 mg to 30 mg of the JAK1 inhibitor. In one aspect, the at least one additional maintenance dose comprises 15 mg or 30 mg. In one aspect, the at least one additional maintenance dose is administered orally. In one aspect, the at least one additional maintenance dose is administered QD. In one embodiment, the at least one additional maintenance dose comprises 15 mg of the JAK1 inhibitor administered QD. In one embodiment, the at least one additional maintenance dose comprises 30 mg of the JAK1 inhibitor administered QD. In one aspect, the at least one additional maintenance dose is in a once-daily modified-release formulation.

[0336] In any of the above-described embodiments, the JAK1 inhibitor can be upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0337] In one aspect of any of the above embodiments, the patient maintains a CDAI score of less than 150.

[0338] In one aspect of any of the above-described embodiments, the patient is one who has had an inadequate response to or experienced intolerance to prior treatment with conventional treatments (e.g., aminosalicylates, corticosteroids, immunosuppressants) or biologic agents. In one aspect of any of the above-described embodiments, the patient is one who has had an inadequate response to or experienced intolerance to prior treatment with an anti-TNF agent. In one aspect of any of the above-described embodiments, the patient is a refractory patient.

[0339] In one aspect of any of the above embodiments, the patient has not been pre-treated with an aminosalicylate, a corticosteroid, an immunosuppressant, a biologic agent, or an anti-TNF agent.

[0340] In one aspect of any of the above embodiments, the patient had moderate to severe active Crohn's disease prior to treatment or administration of the induction dose.

[0341] In one embodiment, the disclosure further provides a method for inducing clinical remission of Crohn's disease in a patient, the method comprising: a) administering to the patient at least one induction dose of a JAK1 inhibitor (e.g., upadacitinib or a pharmaceutically acceptable salt or solid form thereof), as described above or herein. In one embodiment, the induction dose comprises 45 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the induction dose is administered at week 0 and once daily (QD) thereafter for up to 16 weeks (e.g., 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 weeks), and the dose is 45 mg QD. In one embodiment, the method further comprises maintaining clinical remission of Crohn's disease, the method further comprising: b) administering a first maintenance dose of the JAK1 inhibitor to the patient after the final induction dose has been administered; and c) administering at least one additional maintenance dose to the patient as described above or herein. In one embodiment, the at least one additional maintenance dose is administered once daily. In one embodiment, the additional maintenance dose is administered once daily for at least 36 additional weeks, including at least 37 weeks, at least 38 weeks, at least 39 weeks, at least 40 weeks, at least 41 weeks, at least 42 weeks, at least 43 weeks, at least 44 weeks, at least 45 weeks, at least 46 weeks, at least 47 weeks, or at least 48 weeks. In one embodiment, the additional maintenance dose is administered once daily for at least 40 additional weeks. In one embodiment, the maintenance dose is 15 mg or 30 mg QD. In one embodiment, the induction dose and the maintenance dose are administered orally. In one embodiment, the patient has a CDAI score of 220 to 450 prior to administration of the first induction dose. In one embodiment, the patient has moderate to severe active Crohn's disease prior to administration of the first induction dose. In one embodiment, the patient has had an inadequate response to or experienced intolerance to prior treatment with conventional treatments (e.g., aminosalicylates, corticosteroids, immunosuppressants) or biologic agents and / or anti-TNF agents.In one embodiment, the patient has not been pretreated with corticosteroids, immunosuppressants, biologic agents, and / or anti-TNF agents. In one embodiment, clinical remission is achieved within 16 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, clinical remission is achieved within 12 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, clinical remission is achieved within 4 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the patient achieves a CDAI score of less than 150 prior to administration of the first maintenance dose. In one embodiment, the induction dose and maintenance doses are in a once-daily modified-release formulation.

[0342] In one embodiment, the disclosure provides a method for inducing endoscopic remission of Crohn's disease, comprising: (a) administering to a patient at least one induction dose of a JAK1 inhibitor (e.g., upadacitinib or a pharmaceutically acceptable salt or solid form thereof), wherein the induction dose comprises 45 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the induction dose is administered once daily (QD) at week 0 and thereafter for up to 16 weeks (e.g., 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 weeks), and the dose is 45 mg QD. In one embodiment, the method further comprises maintaining endoscopic remission of Crohn's disease, the method further comprising (b) administering a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt or solid form thereof to the patient after the final induction dose has been administered, and (c) thereafter administering at least one additional maintenance dose once daily. In one embodiment, the additional maintenance dose is administered once daily for at least an additional 36 weeks, including at least 37 weeks, at least 38 weeks, at least 39 weeks, at least 40 weeks, at least 41 weeks, at least 42 weeks, at least 43 weeks, at least 44 weeks, at least 45 weeks, at least 46 weeks, at least 47 weeks, or at least 48 weeks. In one embodiment, the additional maintenance dose is administered once daily for at least an additional 40 weeks. In one embodiment, the maintenance dose is 15 mg or 30 mg QD. In one embodiment, the induction dose and maintenance dose are administered orally. In one embodiment, the patient has a CDAI score of 220 to 450 prior to administration of the first induction dose. In one embodiment, the patient has moderate to severe active Crohn's disease prior to administration of the first induction dose. In one embodiment, the patient has had an inadequate response to or experienced intolerance to prior treatment with conventional treatments (e.g., aminosalicylates, corticosteroids, immunosuppressants), or biologic and / or anti-TNF agents. In one embodiment, the patient has not received prior treatment with corticosteroids, immunosuppressants, anti-TNF agents, and / or biologic agents.In one embodiment, endoscopic remission is achieved within 12 weeks or within 16 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt, or solid form thereof. In one embodiment, endoscopic remission is achieved within 4 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt, or solid form thereof. In one embodiment, the patient achieves a CDAI score of less than 150 prior to administration of the first maintenance dose. In one embodiment, the induction dose and maintenance doses are in a once-daily modified-release formulation.

[0343] In one embodiment, the disclosure further provides a method for inducing endoscopic improvement of Crohn's disease in a patient, the method comprising: a) administering to the patient at least one induction dose of a JAK1 inhibitor (e.g., upadacitinib or a pharmaceutically acceptable salt or solid form thereof), as described above or herein. In one embodiment, the induction dose comprises 45 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the induction dose is administered once daily (QD) at week 0 and thereafter for up to 16 weeks (e.g., 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 weeks), and the dose is 45 mg QD. In one embodiment, the method further comprises maintaining endoscopic improvement of Crohn's disease, the method further comprising: b) administering a first maintenance dose of the JAK1 inhibitor to the patient after the final induction dose has been administered; and c) administering at least one additional maintenance dose to the patient as described above or herein. In one embodiment, the at least one additional maintenance dose is administered once daily. In one embodiment, the additional maintenance dose is administered once daily for at least 36 additional weeks, including at least 37 weeks, at least 38 weeks, at least 39 weeks, at least 40 weeks, at least 41 weeks, at least 42 weeks, at least 43 weeks, at least 44 weeks, at least 45 weeks, at least 46 weeks, at least 47 weeks, or at least 48 weeks. In one embodiment, the additional maintenance dose is administered once daily for at least 40 additional weeks. In one embodiment, the maintenance dose is 15 mg or 30 mg QD. In one embodiment, the induction dose and the maintenance dose are administered orally. In one embodiment, the patient has a CDAI score of 220 to 450 prior to administration of the first induction dose. In one embodiment, the patient has moderate to severe active Crohn's disease prior to administration of the first induction dose. In one embodiment, the patient has had an inadequate response to or experienced intolerance to prior treatment with conventional treatments (e.g., aminosalicylates, corticosteroids, immunosuppressants) or biologic agents and / or anti-TNF agents.In one embodiment, the patient has not been pretreated with corticosteroids, immunosuppressants, biologic agents, and / or anti-TNF agents. In one embodiment, endoscopic improvement is achieved within 16 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, endoscopic improvement is achieved within 12 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, endoscopic improvement is achieved within 4 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the patient achieves a CDAI score of less than 150 prior to administration of the first maintenance dose. In one embodiment, the induction dose and maintenance dose are in a once-daily modified-release formulation.

[0344] In one embodiment, the disclosure further provides a method of maintaining clinical remission of Crohn's disease in a patient, comprising administering 15 mg or 30 mg of upadacitinib or a pharmaceutically acceptable salt form thereof to the patient. In one embodiment, upadacitinib or a pharmaceutically acceptable salt form thereof is administered once daily for at least 36 weeks, including at least 37 weeks, at least 38 weeks, at least 39 weeks, at least 40 weeks, at least 41 weeks, at least 42 weeks, at least 43 weeks, at least 44 weeks, at least 45 weeks, at least 46 weeks, at least 47 weeks, or at least 48 weeks. In one embodiment, upadacitinib or a pharmaceutically acceptable salt form thereof is administered orally. In one embodiment, the patient has had an inadequate response to or experienced intolerance to conventional treatments (e.g., aminosalicylates, corticosteroids, immunosuppressants), or prior treatment with biologic agents and / or anti-TNF agents. In one embodiment, the patient has not been pretreated with corticosteroids, immunosuppressants, biologic agents, and / or anti-TNF agents. In one embodiment, the patient is a refractory patient. In one embodiment, upadacitinib or a pharmaceutically acceptable salt form thereof is a once-daily modified-release formulation.

[0345] In one embodiment, the disclosure further provides a method of maintaining endoscopic improvement of Crohn's disease in a patient, comprising administering 15 mg or 30 mg of upadacitinib or a pharmaceutically acceptable salt form thereof to the patient. In one embodiment, upadacitinib or a pharmaceutically acceptable salt form thereof is administered once daily for at least 36 weeks, including at least 37 weeks, at least 38 weeks, at least 39 weeks, at least 40 weeks, at least 41 weeks, at least 42 weeks, at least 43 weeks, at least 44 weeks, at least 45 weeks, at least 46 weeks, at least 47 weeks, or at least 48 weeks. In one embodiment, upadacitinib or a pharmaceutically acceptable salt form thereof is administered orally. In one embodiment, the patient has had an inadequate response to or experienced intolerance to conventional treatments (e.g., aminosalicylates, corticosteroids, immunosuppressants), or prior treatment with biologic agents and / or anti-TNF agents. In one embodiment, the patient has not been pretreated with corticosteroids, immunosuppressants, biologic agents, and / or anti-TNF agents. In one embodiment, the patient is a refractory patient. In one embodiment, upadacitinib or a pharmaceutically acceptable salt form thereof is a once-daily modified-release formulation.

[0346] In one embodiment, the disclosure further provides a method of maintaining endoscopic remission of Crohn's disease in a patient, comprising administering 15 mg or 30 mg of upadacitinib or a pharmaceutically acceptable salt form thereof to the patient. In one embodiment, upadacitinib or a pharmaceutically acceptable salt form thereof is administered once daily for at least 36 weeks, including at least 37 weeks, at least 38 weeks, at least 39 weeks, at least 40 weeks, at least 41 weeks, at least 42 weeks, at least 43 weeks, at least 44 weeks, at least 45 weeks, at least 46 weeks, at least 47 weeks, or at least 48 weeks. In one embodiment, upadacitinib or a pharmaceutically acceptable salt form thereof is administered orally. In one embodiment, the patient has had an inadequate response to or experienced intolerance to conventional treatments (e.g., aminosalicylates, corticosteroids, immunosuppressants), or prior treatment with biologic agents and / or anti-TNF agents. In one embodiment, the patient has not been pretreated with corticosteroids, immunosuppressants, biologic agents, and / or anti-TNF agents. In one embodiment, the patient is a refractory patient. In one embodiment, upadacitinib or a pharmaceutically acceptable salt form thereof is a once-daily modified-release formulation.

[0347] In one embodiment, the disclosure further provides a method of maintaining remission of Crohn's disease in a patient, comprising administering 15 mg or 30 mg of upadacitinib or a pharmaceutically acceptable salt form thereof to the patient. In one embodiment, upadacitinib or a pharmaceutically acceptable salt form thereof is administered once daily for at least 36 weeks, including at least 37 weeks, at least 38 weeks, at least 39 weeks, at least 40 weeks, at least 41 weeks, at least 42 weeks, at least 43 weeks, at least 44 weeks, at least 45 weeks, at least 46 weeks, at least 47 weeks, or at least 48 weeks. In one embodiment, upadacitinib or a pharmaceutically acceptable salt form thereof is administered orally. In one embodiment, the patient has had an inadequate response to or experienced intolerance to conventional treatments (e.g., aminosalicylates, corticosteroids, immunosuppressants), or prior treatment with biologic agents and / or anti-TNF agents. In one embodiment, the patient has not been pretreated with a corticosteroid, an immunosuppressant, a biologic agent, and / or an anti-TNF agent. In one embodiment, the patient is a resistant patient. In one embodiment, upadacitinib or a pharmaceutically acceptable salt form thereof is a salt form in a once-daily modified-release formulation.

[0348] In one embodiment, the induction dose for the methods disclosed herein is administered for 12 weeks at a dosing regimen set forth in Table 3. In one embodiment, the induction dose is administered for 16 weeks at a dosing regimen set forth in Table 3. In one embodiment, the maintenance dose is administered for 36 weeks or more at a dosing regimen set forth in Table 3. In one embodiment, the induction dose for the methods disclosed herein is administered for 16 weeks and the maintenance dose is administered for 36 weeks at a dosing regimen set forth in Table 3.

[0349] [Table 3]

[0350] In one embodiment, the induction dose for the methods disclosed herein is administered for two weeks using a dosing regimen set forth in Table 4. In one embodiment, the induction dose for the methods disclosed herein is administered for four weeks using a dosing regimen set forth in Table 4. In one embodiment, the induction dose for the methods disclosed herein is administered for 12 weeks using a dosing regimen set forth in Table 4. In one embodiment, the induction dose for the methods disclosed herein is administered for 16 weeks using a dosing regimen set forth in Table 4. In one embodiment, the maintenance dose is administered for 36 weeks or more using a dosing regimen set forth in Table 4. In one embodiment, the induction dose for the methods disclosed herein is administered for two weeks and the maintenance dose is administered for 36 or 40 weeks using a dosing regimen set forth in Table 4. In one embodiment, the induction dose for the methods disclosed herein is administered for four weeks and the maintenance dose is administered for 36 or 40 weeks using a dosing regimen set forth in Table 4. In one aspect, the induction dose for the methods disclosed herein is administered for 12 weeks and the maintenance dose for 36 or 40 weeks in the dosing regimen set forth in Table 4. In one aspect, the induction dose for the methods disclosed herein is administered for 16 weeks and the maintenance dose for 36 or 40 weeks in the dosing regimen set forth in Table 4.

[0351] [Table 4]

[0352] In one particular embodiment, the induction dose is 45 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof administered QD, and the maintenance dose, and any additional maintenance doses administered thereafter, are 30 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof administered QD. In another embodiment, the induction dose is 45 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof administered QD, and the maintenance dose, and any additional maintenance doses administered thereafter, are 15 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof administered QD. In one embodiment, the maintenance dose and the induction dose are in a once-daily modified-release formulation.

[0353] IV. Methods of Treating Ulcerative Colitis In one aspect, the present disclosure is directed to a method for treating ulcerative colitis. In one aspect, the present disclosure provides a method for treating ulcerative colitis, particularly a method comprising administering a JAK1 inhibitor to a patient in a specific amount and / or at a specific interval. In one aspect, the JAK1 inhibitor is upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0354] In one aspect, the disclosure provides a JAK1 inhibitor for use in treating ulcerative colitis by administration in a certain amount and / or at certain intervals, as described herein. In one aspect, the JAK1 inhibitor is upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0355] In one aspect, the disclosure provides use of a JAK1 inhibitor for preparing a medicament for the treatment of ulcerative colitis by administering a specific amount and / or at specific intervals, as described herein, hi one aspect, the JAK1 inhibitor is upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0356] In one aspect, the present disclosure is directed to a method for inducing clinical and / or endoscopic remission of ulcerative colitis. In one aspect, the present disclosure provides a method for inducing clinical and / or endoscopic remission of ulcerative colitis, particularly a method comprising administering a JAK1 inhibitor to a patient in a certain amount and / or at certain intervals, as described herein. In one aspect, the present disclosure is further directed to a method for inducing clinical remission, wherein the patient has an SF score of ≦1, an RBS of 0, and an endoscopy score of ≦1 at 48 weeks after administration of the JAK1 inhibitor. In one aspect, the patient achieves clinical remission according to a complete Mayo score of ≦2 with no subscores >1, plus fecal calprotectin of less than 150 mg / kg at 8 weeks after administration of the JAK1 inhibitor. In one aspect, the patient has an increase from baseline in IBDQ of ≧16 at 8 weeks after administration of the JAK1 inhibitor. In one embodiment, the patient has an RBS > 1 or an absolute RBS < 1 at 8 weeks after administration of the JAK1 inhibitor. In one embodiment, the patient has an SF subscore < 1 at 8 weeks after administration of the JAK1 inhibitor. In one embodiment, the patient achieves an RBS of 0 at week 8. In one embodiment, the patient achieves a fecal calprotectin of less than 150 mg / kg at 8 weeks after administration of the JAK1 inhibitor. In one embodiment, the patient achieves histological improvement at 8 weeks after administration of the JAK1 inhibitor. In one embodiment, the JAK1 inhibitor is upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0357] In one aspect, the disclosure provides a JAK1 inhibitor for use in inducing clinical remission of ulcerative colitis by administration in a certain amount and / or at certain intervals, as described herein. In one aspect, the disclosure provides a JAK1 inhibitor for use in inducing clinical remission and / or clinical response and / or endoscopic improvement and / or endoscopic remission of ulcerative colitis by administration in a certain amount and / or at certain intervals, as described herein. In one aspect, the JAK1 inhibitor is upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0358] In one aspect, the disclosure provides use of a JAK1 inhibitor for the preparation of a medicament for inducing clinical remission of ulcerative colitis by administration in a certain amount and / or at certain intervals, as described herein. In one aspect, the disclosure provides use of a JAK1 inhibitor for the preparation of a medicament for inducing clinical remission and / or clinical response and / or endoscopic improvement and / or endoscopic remission of ulcerative colitis by administration in a certain amount and / or at certain intervals, as described herein. In one aspect, the JAK1 inhibitor is upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0359] In one particular aspect, the disease is moderate to severe active ulcerative colitis. In one aspect, in the context of the present disclosure, the patient has not received or has previously been treated with immunosuppressants (e.g., methotrexate), aminosalicylates, corticosteroids, and / or biologic agents (e.g., vedolizumab, ustekinumab, natalizumab, etc.). In one aspect, the patient has not received or has previously been treated with anti-TNF therapy (e.g., infliximab, adalimumab, certolizumab pegol, golimumab, etc.). In one aspect, in the context of the method of the present invention, the patient has previously been treated with one, two, three or more TNF antagonists (also referred to herein as anti-TNF agents). In one embodiment, the patient is a patient who has had an inadequate response, lost response, or was intolerant to a TNF antagonist. In one aspect of the context of the method of the present invention, the patient has previously been treated with one, two, three or more biological agents. In one embodiment, the patient is a patient who has had an inadequate response, lost response, or is intolerant to the biological agents. In one embodiment, the patient is a patient who has had an inadequate response, lost response, or is intolerant to TNF antagonists, aminosalicylates, corticosteroids, immunosuppressants, and / or biological agents. In one embodiment, the patient is a resistant patient with moderate to severe active ulcerative colitis. In one embodiment, the patient is either not receiving or has discontinued the use of corticosteroids prior to treatment with a JAK1 inhibitor.

[0360] Ulcerative colitis disease severity was assessed using the Mayo Score System for Assessment of Ulcerative Colitis Activity ("Full Mayo"), the adapted Mayo score (consisting of the Full Mayo stool frequency subscore, rectal bleeding subscore, and endoscopy subscore), the Ulcerative Colitis Severity Endoscopic Index (UCEIS) score system, the Inflammatory Bowel Disease Questionnaire (IBDQ), the Ulcerative Colitis Work Productivity and Activity Impairment Questionnaire (version 2.0) (WPAI:UC), the European Quality of Life 5 Dimensions 5 Levels (EQ-5D-5L), the Short Form 36 Item (SF-36) Health Survey (version 2), the Functional Assessment of Chronic Illness Treatment Fatigue (FACIT-F), the Ulcerative Colitis Symptom Questionnaire (UC-SQ), and the Patient Global Impression of Change (PGC). This can be measured using a variety of indices, including Prognostic Change (PGIC).

[0361] The Mayo scoring system for assessment of ulcerative colitis activity, shown below, is a composite of the following subscores: stool frequency subscore, rectal bleeding subscore (RBS), endoscopy subscore, and physician's global assessment subscore.

[0362] [Table 5]

[0363] The IBDQ is a well-known, validated 32-item questionnaire that assesses a patient's inflammatory bowel disease symptoms, general well-being, and mood, and can be used as a tool to evaluate a patient's quality of life (Guyatt et al., Gastroenterology, 1989, 96:804-810). The IBDQ questions and answer options are listed in Table 6 below.

[0364] [Table 6] TIFF2026041823000008.tif238170TIFF2026041823000009.tif238170TIFF2026041823000010.tif240170TIFF2026041823000011.tif211170

[0365] The Work Productivity and Activity Impairment Questionnaire for Ulcerative Colitis (WPAI:UC) and Crohn's Disease (WPAI:CD) assesses the impact of the condition on work productivity loss and impairment of daily activities. The WPAI:UC has six items covering four domains of absenteeism (work time lost) measured as time missed from work during the past seven days due to problems related to the condition. Scores are expressed as a percentage disability adjusted for hours actually worked according to the WPAI:UC or WPAI:CD scoring algorithm; sickness working (impairment at work / reduced effectiveness at work) measured as the impact of the condition on productivity at work (i.e., reduced amount or type of work, or inability to concentrate as well as normal). Responses are recorded on a 0-10 Likert scale (where 0 = no effect of UC or CD on work and 10 = severe impact of UC or CD at work), time lost due to the condition, i.e., absenteeism, and time worked with disability, i.e., productivity loss (total work disability), measured as the sum of the product of hours worked and sickness work, and activity impairment (i.e., activities other than paid work, such as housework, cleaning, shopping, travel, and study), recorded and scored in the same manner as sickness work. Higher values ​​indicate greater impairment and less productivity. The WPAI:UC / WPAI:CD questions and answer options are listed in Table 7.

[0366] [Table 7]

[0367] The European Quality of Life 5-item, 5-level scale (EQ-5D-5L) is a standardized, non-disease-specific instrument for describing and assessing health-related quality of life. The EQ-5D-5L consists of five items: mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. Each item has five levels: no problems, slight problems, moderate problems, severe problems, or inability to function. It also includes a visual analogue scale (VAS). For each item, subjects are asked to indicate the level that describes their current level of functioning or experience. A descriptive profile is provided as a measure of health status, which can be used to generate a single index value for health status (where perfect health equals 1 and death equals 0). The VAS involves recording subjects' own assessment of their health along a 20-cm vertical line with a health status score ranging from 0 to 100. The EQ-5D-5L questions and answer options are listed in Table 8.

[0368] [Table 8]

[0369] The SF-36 questionnaire is a self-administered multidomain scale containing 36 items. It encompasses a variety of functions through eight subscales: physical functioning (PF), role functioning (physical) (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role functioning (emotional) (RE), and mental health (MH). Scoring yields a physical component score, a mental component summary score, and subscale scores. Higher scores represent better outcomes. The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, allowing comparisons of the relative burden of various diseases and the benefits of various treatments. The SF-36 questions and answer options are shown in Table 9 below.

[0370] [Table 9] TIFF2026041823000015.tif239170TIFF2026041823000016.tif238170TIFF2026041823000017.tif177170

[0371] The Functional Assessment of Chronic Illness Therapy (FACIT) system is a collection of quality of life (QOL) questionnaires targeted at the management of cancer and other chronic diseases. The FACIT-Fatigue (FACIT-F) questionnaire was developed to assess fatigue associated with anemia. This questionnaire consists of 13 questions related to fatigue. Responses to each of the 13 FACIT-Fatigue items are measured on a 4-point Likert scale. Responses are as follows: (i) not at all fatigued: 0 points; (ii) slightly fatigued: 1 point; (iii) slightly fatigued: 2 points; (iv) very fatigued: 3 points; and (v) very fatigued: 4 points. Thus, the total score ranges from 0 to 52. Higher scores represent less fatigue. The FACIT-F questions and answer options are shown in Table 10 below.

[0372] [Table 10]

[0373] The Ulcerative Colitis Symptom Questionnaire (UC-SQ) is a 17-item Likert-type instrument specific to UC. The UC-SQ was developed to assess gastrointestinal and non-gastrointestinal symptoms associated with UC, such as frequent bowel movements, abdominal discomfort, nausea, loss of appetite, pain, and anemia, along with the impact on patients' sleep. Each question can be answered using Likert-type options based on how the patient felt during the past week (i.e., 7 days): (i) not at all: 0 points; (ii) slightly: 1 point; (iii) a little: 2 points; (iv) quite a lot: 3 points; and (v) very much: 4 points. The total score range can vary from 0 to 68, with lower scores indicating greater improvement. The UC-SQ questions and answer options are shown in Table 11 below.

[0374] [Table 11]

[0375] The Patient Global Impression of Change (PGIC) is a self-administered instrument that assesses change in overall ulcerative colitis symptoms. The PGIC is a single item that asks patients to rate their overall improvement since treatment began. Patients are asked the question, "How would you rate the change in your overall ulcerative colitis symptoms compared to before treatment began?" and rate their change as "very improved," "much improved," "minimally improved," "no change," "minimally worsened," "much worsened," and "very worsened."

[0376] In one embodiment, the patient to be treated has moderately to severely active ulcerative colitis, characterized by an adapted Mayo score of 5 to 9 points and an endoscopy subscore of 2 to 3.

[0377] In one embodiment, the patient has had an inadequate response, lost response, or been intolerant to conventional therapy (e.g., aminosalicylates, corticosteroids, immunosuppressants) or biologic agents. In one embodiment, the patient has had an inadequate response, lost response, or been intolerant to biologic therapy. Examples of such biologic therapy include infliximab, adalimumab, vedolizumab, golimumab, ustekinumab, and certolizumab pegol. The criteria for determining whether a patient has had an inadequate response, lost response, or experienced intolerance to prior treatment with corticosteroids, immunosuppressants, and / or biologic therapy are defined below.

[0378] Corticosteroids 1) persistently active signs and symptoms of disease despite a history of at least one induction regimen that included prednisone ≥ 40 mg / day equivalent orally for 3-4 weeks or intravenously for 1 week; or 2) Inability to taper corticosteroids to less than 10 mg oral prednisone equivalent per day without recurrence of active disease, or 3) History of intolerance to corticosteroids (including but not limited to Cushing's syndrome, osteopenia / osteoporosis, hyperglycemia, insomnia, infection).

[0379] immunosuppressants 1) Oral azathioprine (≥ 1.5 mg / kg / day; for Japanese and Chinese subjects only, ≥ 1.0 mg / kg / day), 6-mercaptopurine (≥ 1 mg / kg / day [for Japanese and Chinese subjects only, ≥ 0.6 mg / kg / day, rounded to the nearest available tablet for half-tablet formulations]), or demonstrated 6-TGN levels of 230–450 pmol / 8 × 10 on the current dosing regimen 8 RBC or more), injectable methotrexate (MTX ≥ 15 mg / week subcutaneously [SC] or intramuscularly), or tacrolimus (for Japanese subjects only, documented trough levels 5–10 ng / mL), or persistently active signs and symptoms of disease despite a history of at least one 90-day regimen of methotrexate (MTX ≥ 15 mg / week subcutaneously [SC] or intramuscularly). 2) History of intolerance to at least one immunosuppressant (including but not limited to nausea / vomiting, abdominal pain, pancreatitis, liver enzyme abnormalities, lymphopenia, infection).

[0380] Biologic Agents for UC 1) Persistent signs and symptoms of active disease despite a history of any of the following: At least one 6-week induction regimen of infliximab (≥ 5 mg / kg intravenously [IV] at weeks 0, 2, and 6), b. At least one 4-week induction regimen of adalimumab (one 160 mg dose SC followed by one 80 mg dose SC [or one 80 mg dose SC followed by one 40 mg dose SC in countries where this dosing regimen is approved], separated by at least 2 weeks), c. At least one 2-week induction regimen of golimumab (one 200 mg dose SC followed by one 100 mg dose SC at least 2 weeks apart), d. At least one 6-week induction regimen of vedolizumab (300 mg IV at weeks 0, 2, and 6), or 2) recurrence of symptoms during maintenance treatment planned according to previous clinical benefit (withdrawal despite clinical benefit is not permitted); or 3) History of intolerance to at least one biologic agent (including but not limited to infusion reactions, demyelination, congestive heart failure (CHF), infection).

[0381] In one embodiment, the patient is one who has been previously treated or is currently undergoing treatment with an aminosalicylate, an immunosuppressant, a corticosteroid and / or a biologic agent.

[0382] In one aspect, the Mayo score system for assessment of ulcerative colitis activity, or any of the assessments described herein above or in the Examples herein below, is used to assess the effectiveness of upadacitinib in treating ulcerative colitis, e.g., moderately to severely active ulcerative colitis. In one embodiment, the assessment used to assess the effectiveness of upadacitinib in treating ulcerative colitis is selected from the group consisting of the complete Mayo score, partial Mayo score, adapted Mayo score, IBDQ, WPAI:UC, EQ-5D-5L, SF-36, FACIT-F, UC-SQ, PGIC, and combinations thereof.

[0383] In one embodiment of the present disclosure, treatment of a patient with ulcerative colitis and / or induction of clinical remission of ulcerative colitis in a patient and / or induction of clinical response and / or endoscopic improvement and / or endoscopic remission includes an induction phase and a maintenance phase. In the induction phase, one or more doses of a JAK1 inhibitor, e.g., referred to herein as induction doses, are administered to the patient, e.g., orally. In the maintenance phase, a first dose of a JAK1 inhibitor, e.g., referred to herein as a maintenance dose, is administered to the patient, followed by at least one additional dose of a JAK1 inhibitor, e.g., also referred to herein as a maintenance dose. The maintenance dose is administered, e.g., orally. The JAK1 inhibitor can be, e.g., upadacitinib or a pharmaceutically acceptable salt or solid form thereof. Examples of induction and maintenance phases are described herein.

[0384] In one aspect, a certain therapeutic outcome, e.g., clinical remission, is achieved by the patient during or at the end of the induction phase. In other embodiments, the therapeutic outcome achieved by the patient during or at the end of the induction phase is selected from the group consisting of an endoscopic subscore of 0 or 1 at week 8, an endoscopic subscore of 0 at week 8, fecal calprotectin less than 150 mg / kg at week 8, an IBDQ response (IBDQ increase from baseline ≧16) at week 8, an RBS ≧1 or absolute RBS ≦1 at week 8, or an RBS of 0 at week 8. In one aspect, the patient achieves clinical remission during or by the end of the induction phase. In one aspect, the patient achieves endoscopic remission during or by the end of the induction phase.

[0385] In one aspect, the patient achieves endoscopic improvement of the ulcerative colitis during or by the end of the induction phase. In one aspect, the patient achieves clinical remission and endoscopic improvement of the ulcerative colitis during or at the end of the induction phase.

[0386] In one embodiment, the induction phase lasts for up to 16 weeks (e.g., up to 16 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof). Thus, in one embodiment, the induction phase is 16 weeks. In another embodiment, the induction phase optionally lasts for less than 16 weeks, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 weeks. In one aspect, the patient achieves endoscopic remission within 8 weeks, or within 12 weeks, or within 16 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one aspect, the patient achieves clinical remission within 8 weeks, or within 12 weeks, or within 16 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the patient achieves endoscopic improvement within 8 weeks, or within 12 weeks, or within 16 weeks after initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the patient achieves clinical response within 8 weeks, or within 12 weeks, or within 16 weeks after initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the patient achieves clinical remission within 8 weeks, or within 12 weeks, or within 16 weeks after initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0387] In one embodiment, the patient achieves clinical remission within two weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the patient achieves clinical remission within four weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0388] In one embodiment, the patient achieves a clinical response within two weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the patient achieves a clinical response within four weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0389] In one embodiment, the patient achieves endoscopic improvement or endoscopic remission within two weeks after initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the patient achieves endoscopic improvement or endoscopic remission within four weeks after initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the patient achieves endoscopic improvement or endoscopic remission within 12 weeks after initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the patient achieves endoscopic improvement or endoscopic remission within 16 weeks after initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.

[0390] In one embodiment, the patient achieves corticosteroid-free remission within 12 weeks after initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the patient achieves corticosteroid-free remission within 8 weeks after initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the corticosteroid-free remission is clinical remission. In one embodiment, the corticosteroid-free remission is endoscopic remission.

[0391] In some embodiments, during or by the end of the induction phase (e.g., including 2 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks, or 16 weeks, continuing up to 16 weeks), the patient achieves at least one therapeutic outcome selected from the group consisting of: 1) Endoscopic improvement (defined as an endoscopic subscore ≤1 within 8 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof), 2) A complete Mayo score ≤2 with no subscore >1 within 8 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof; 3) Clinical response (defined as a reduction from baseline in the adapted Mayo score of ≥ 2 points and a reduction from baseline of ≥ 30% plus a reduction in the rectal bleeding subscore (RBS) of ≥ 1, or an absolute RBS of 0 or 1) within 8 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof; 4) Clinical response within 2 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; 5) Change from baseline in complete Mayo score through 8 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; 6) Endoscopic remission (defined as an endoscopic subscore of 0) within 8 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 7) Histological improvement (defined as a reduction from baseline in Geboes score) within 8 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 8) A decrease in RBS ≥ 1 or absolute RBS ≤ 1 within 8 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; 9) RBS of 0 within 8 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof; 10) Endoscopic improvement (endoscopic subscore of 0 or 1) within 8 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 11) A stool frequency subscore of ≤1 within 8 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; 12) Maintenance of clinical remission at 52 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof in patients who achieved clinical remission within 8 weeks of initiating upadacitinib or a pharmaceutically acceptable salt or solid form thereof; 13) Endoscopic improvement within 52 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 14) Complete Mayo score ≤2 with no subscore >1 within 52 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof; 15) Clinical remission within 52 weeks after initiating treatment with upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, in patients who discontinued corticosteroid use prior to initiation of treatment with upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; 16) Subjects taking corticosteroids at baseline and have not used steroids within 52 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 17) Endoscopic improvement at 52 weeks after initiation of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, in patients who achieved clinical remission within 8 weeks of initiation of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; 18) Clinical response within 44 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 19) Endoscopic remission within 52 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 20) Histological improvement within 52 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. 21) clinical remission according to adapted Mayo score (defined as SFS ≤ 1, RBS of 0, and endoscopic subscore ≤ 1); and combinations thereof.

[0392] In some embodiments, the patient achieves clinical remission within 16 weeks or within 12 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, and also achieves any combination of an additional therapeutic outcome selected from the group consisting of therapeutic outcomes 1), 2), 3), 4), 5), 6), 7), 8), 9), 10), 11), 12), 13), 14), 15), 16), 17), 18), 19), 20), 21), and combinations thereof. In one such embodiment, the induction phase is 16 weeks. In one embodiment, the additional therapeutic outcome is achieved within 8 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, and is selected from the group consisting of therapeutic outcomes 1), 2), 3), 4), 5), 6), 7), 8), 9), 10), 11), and combinations thereof.

[0393] In one embodiment, the induction phase is 8 weeks long and the patient achieves clinical remission within 8 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, and also achieves any combination of an additional therapeutic outcome selected from the group consisting of therapeutic outcomes 1), 2), 3), 4), 5), 6), 7), 8), 9), 10), 11), 12), 13), 14), 15), 16), 17), 18), 19), 20), 21), and combinations thereof. In one embodiment, the additional therapeutic outcome is achieved within 8 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the additional therapeutic outcome is achieved within 8 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof and is selected from the group consisting of therapeutic outcomes 1), 2), 3), 4), 5), 6), 7), 8), 9), 10), 11), and combinations thereof.

[0394] In one embodiment, the induction phase is 4 weeks long, and the patient achieves clinical remission within 4 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, and also achieves any combination of an additional therapeutic outcome selected from the group consisting of therapeutic outcomes 1), 2), 3), 4), 5), 6), 7), 8), 9), 10), 11), 12), 13), 14), 15), 16), 17), 18), 19), 20), 21), and combinations thereof. In one embodiment, the additional therapeutic outcome is achieved within 4 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the additional therapeutic outcome is achieved within 4 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, and is selected from the group consisting of endoscopic improvement, clinical remission, clinical response, endoscopic remission, histologic improvement, and combinations thereof.

[0395] In one embodiment, the patient achieves clinical remission within 4 weeks, 8 weeks, 12 weeks, or 16 weeks of initiating upadacitinib or a pharmaceutically acceptable salt or solid form thereof, and / or achieves endoscopic improvement within 4 weeks, 8 weeks, 12 weeks, or 16 weeks of initiating upadacitinib or a pharmaceutically acceptable salt or solid form thereof, and further achieves a ≥ 2-point reduction from baseline in partial Mayo score over time and a ≥ 2-point reduction from baseline in partial Mayo score over time within 16 weeks of initiating upadacitinib or a pharmaceutically acceptable salt or solid form thereof. a ≥ 30% reduction from baseline in the partial Mayo score over time plus a reduction in RBS of ≥ 1 or an absolute RBS ≤ 1; a clinical response according to partial Mayo score within 12 weeks after initiation of treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof; a ≥ 2-point reduction from baseline in partial Mayo score over time and a ≥ 30% reduction from baseline plus a reduction in RBS of ≥ 1 or an absolute RBS ≤ 1 within 8 weeks after initiation of treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof a reduction from baseline in partial Mayo score over time of ≥ 2 points and a reduction from baseline of ≥ 30% from baseline, plus a reduction in RBS of ≥ 1 or an absolute RBS of ≤ 1, within 4 weeks after initiation of treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof; a reduction from baseline in partial Mayo score over time of ≥ 2 points and a reduction from baseline of ≥ 30% from baseline, plus a reduction in RBS of ≥ 1 or an absolute RBS of ≤ 1, within 2 weeks after initiation of treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof; resolution; endoscopic remission within 12 weeks after initiation of treatment with upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; endoscopic remission within 8 weeks after initiation of treatment with upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; endoscopic remission within 4 weeks after initiation of treatment with upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; clinical response within 16 weeks after initiation of treatment with upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; clinical response within 12 weeks after initiation of treatment with upadacitinib, or a pharmaceutically acceptable salt or solid form thereof;Clinical response within 8 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof; clinical response within 4 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof; complete Mayo score ≤ 2 with no subscore > 1 within 16 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof; complete Mayo score ≤ 2 with no subscore > 1 within 12 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof; Complete Mayo score ≤ 2 with no subscore > 1 within 8 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof; Complete Mayo score ≤ 2 with no subscore > 1 within 4 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof; Endoscopic improvement within 16 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof; Endoscopic improvement within 12 weeks of initiating treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof; endoscopic improvement within 8 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; endoscopic improvement within 4 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; a reduction in RBS of ≥ 1 or a reduction from baseline in complete Mayo score of ≥ 3 points and ≥ 30% with an absolute RBS of 0 or 1 within 16 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; a reduction in RBS of ≥ 1 or an absolute RBS of 0 or 1 within 12 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof a reduction from baseline in complete Mayo score of ≥ 3 points and ≥ 30% with a reduction in RBS of ≥ 1 or an absolute RBS of 0 or 1 within 8 weeks of initiating upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; a reduction from baseline in complete Mayo score of ≥ 3 points and ≥ 30% with a reduction in RBS of ≥ 1 or an absolute RBS of 0 or 1 within 4 weeks of initiating upadacitinib, or a pharmaceutically acceptable salt or solid form thereof;and combinations thereof. In one embodiment, the patient achieves clinical remission within 12 weeks or within 16 weeks after initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof and / or achieves clinical remission according to an adapted Mayo score (defined as an SFS≦1, an RBS of 0, and an endoscopy subscore≦1) within 12 weeks after initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the patient achieves a clinical response according to an adapted Mayo score (defined as an adapted Mayo score reduction from BL of ≧2 points and a reduction from BL of ≧30% at week 12 or week 16, plus an RBS reduction of ≧1 or an absolute RBS≦1). In one such embodiment, the induction phase is 16 weeks long and additional treatment outcomes include a reduction from baseline in partial Mayo score over time of ≧2 points and a reduction from baseline of ≧30% within 16 weeks, 12 weeks, 8 weeks, 4 weeks, or 2 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, as well as a reduction in RBS of ≧1 or absolute RBS≦1; endoscopic remission within 16 weeks, 12 weeks, 8 weeks, or 4 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; clinical response within 16 weeks, 12 weeks, 8 weeks, or 4 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; endoscopic improvement within 16 weeks, 12 weeks, 8 weeks, or 4 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; complete Mayo score ≤ 2 with no subscore > 1 within 16 weeks, 12 weeks, 8 weeks, or 4 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; a reduction in RBS ≥ 1, or a reduction from baseline in complete Mayo score ≥ 3 points and ≥ 30% with an absolute RBS of 0 or 1 within 16 weeks, 12 weeks, 8 weeks, or 4 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof;and combinations thereof. In one such embodiment, the induction phase is 12 weeks and the additional treatment outcomes include a reduction from baseline in partial Mayo score over time of ≥ 2 points and a reduction from baseline of ≥ 30% as well as a reduction in RBS of ≥ 1 or absolute RBS ≤ 1 within 12 weeks, 8 weeks, 4 weeks, or 2 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; endoscopic remission within 12 weeks, 8 weeks, or 4 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; clinical remission within 12 weeks, 8 weeks, or 4 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; endoscopic response; endoscopic improvement within 12 weeks, 8 weeks, or 4 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; a complete Mayo score of ≦2 with no subscore >1 within 12 weeks, 8 weeks, or 4 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; a reduction in RBS of ≧1, or a reduction from baseline in the complete Mayo score of ≧3 points and ≧30% with an absolute RBS of 0 or 1 within 12 weeks, 8 weeks, or 4 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; and combinations thereof. In one such embodiment, the induction phase is 8 weeks long and additional treatment outcomes include a reduction from baseline in partial Mayo score over time of ≧2 points and a reduction from baseline of ≧30% within 48 weeks, 8 weeks, 4 weeks, or 2 weeks after initiation of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, as well as a reduction in RBS of ≧1 or absolute RBS≦1; endoscopic remission within 8 weeks or 4 weeks after initiation of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; clinical response within 8 weeks or 4 weeks after initiation of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; endoscopic improvement within 8 weeks or 4 weeks after initiation of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; a complete Mayo score≦2 with no subscores >1 within 8 weeks or 4 weeks after initiation of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof;a reduction in RBS of ≥ 1, or a reduction from baseline in complete Mayo score of ≥ 3 points and ≥ 30% with an absolute RBS of 0 or 1, within 8 weeks or within 4 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; and combinations thereof.

[0396] In one embodiment, the patient achieves clinical remission within 16 weeks, or within 12 weeks, or within 8 weeks, or within 4 weeks after initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one such embodiment, the patient was taking corticosteroids at baseline but discontinued corticosteroids during treatment with the JAK1 inhibitor.

[0397] In one embodiment, an additional treatment outcome can be a complete Mayo score < 2 with no subscores > 1 within 16 weeks, or within 12 weeks, or within 8 weeks, or within 4 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one such embodiment, the patient was taking corticosteroids at baseline but discontinued corticosteroids during treatment with the JAK1 inhibitor. In another embodiment, the additional treatment outcomes include endoscopic remission within 16 weeks, within 12 weeks, within 8 weeks, or within 4 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; clinical response within 16 weeks, or within 12 weeks, or within 8 weeks, or within 4 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; a ≥ 2-point reduction from baseline in partial Mayo score over time and a ≥ 2-point reduction from baseline in partial Mayo score over time within 16 weeks, or within 12 weeks, or within 8 weeks, or within 4 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. a reduction in RBS of ≥ 1 or an absolute RBS of ≤ 1 in addition to a ≥ 30% reduction from baseline; a reduction in RBS of ≥ 1, or a reduction in complete Mayo score of ≥ 3 points and ≥ 30% from baseline with an absolute RBS of 0 or 1 within 16 weeks, or within 12 weeks, or within 8 weeks, or within 4 weeks of initiating upadacitinib or a pharmaceutically acceptable salt or solid form thereof; and endoscopic improvement within 16 weeks, or within 12 weeks, or within 8 weeks, or within 4 weeks of initiating upadacitinib or a pharmaceutically acceptable salt or solid form thereof; and combinations thereof. In one such embodiment, the patient was taking corticosteroids at baseline but discontinued corticosteroids during treatment with the JAK1 inhibitor.

[0398] In one embodiment, an additional treatment outcome can be an adapted Mayo score (defined as an SFS≦1, an RBS of 0, and an endoscopy subscore≦1) at week 16, or within 12 weeks, or within 8 weeks after initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one such embodiment, the patient was taking corticosteroids at baseline but discontinued corticosteroids during treatment with the JAK1 inhibitor. In another embodiment, the additional treatment outcomes include endoscopic remission within 16 weeks, within 12 weeks, or within 8 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; clinical response within 16 weeks, within 12 weeks, or within 8 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; a reduction from baseline in partial Mayo score over time of ≥ 2 points and a reduction from baseline of ≥ 30 points within 16 weeks, within 12 weeks, or within 8 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. %, the patient may be selected from the group consisting of a reduction in RBS of ≥ 1 or an absolute RBS ≤ 1; a reduction in RBS of ≥ 1, or a reduction from baseline in complete Mayo score of ≥ 3 points and ≥ 30% with an absolute RBS of 0 or 1 within 16 weeks, or within 12 weeks, or within 8 weeks, or within 4 weeks of initiating upadacitinib or a pharmaceutically acceptable salt or solid form thereof; and endoscopic improvement within 16 weeks, or within 12 weeks, or within 8 weeks, or within 4 weeks of initiating upadacitinib or a pharmaceutically acceptable salt or solid form thereof; and combinations thereof. In one such embodiment, the patient was taking corticosteroids at baseline but discontinued corticosteroids during treatment with the JAK1 inhibitor.

[0399] In one particular embodiment, the induction phase is 8 weeks long, and patients achieve clinical remission (SF subscore < 1, RBS of 0, and endoscopic subscore < 1) within 8 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, and achieve endoscopic improvement (i.e., endoscopic subscore < 1) within 6 weeks or within 8 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In another embodiment, the induction phase is 4 weeks long, and patients achieve clinical remission within 4 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, and achieve endoscopic improvement within 4 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0400] In one particular embodiment, the induction phase is 8 weeks long, and the patient achieves clinical remission within 8 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, and further achieves a complete Mayo score of ≦2 with no subscores >1 within 8 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; endoscopic improvement (i.e., an endoscopic subscore ≦1) within 6 weeks or within 8 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, or a combination thereof. In another embodiment, the induction phase is 4 weeks, and the patient achieves clinical remission within 4 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, and further achieves a complete Mayo score of ≦2 with no subscores >1 within 4 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; endoscopic improvement within 4 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; or a combination thereof.

[0401] In one embodiment, the patient is administered upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, for at least 52 weeks. Administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, may include an induction phase (e.g., an induction phase of up to 16 weeks) and an additional week (e.g., 36 weeks or more) of maintenance phase (discussed below). In other embodiments, administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, may include a shorter induction phase (e.g., up to 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks, etc.) and a longer maintenance phase (e.g., a 12-week induction phase and a 40-week or more maintenance phase).

[0402] In one embodiment, the induction phase is 8 weeks and the maintenance phase is 44 weeks. In some such embodiments, patients achieve: clinical remission within 52 weeks after initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; endoscopic remission within 52 weeks after initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; complete Mayo score < 2 with no subscore > 1 within 52 weeks after initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; Clinical response within 52 weeks after initiation of treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof; endoscopic improvement within 52 weeks after initiation of treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof; a reduction from baseline in partial Mayo score over time of ≥ 2 points and a reduction from baseline of ≥ 30% plus a reduction in RBS of ≥ 1 or absolute RBS of ≤ 1 within 52 weeks after initiation of treatment with upadacitinib or a pharmaceutically acceptable salt or solid form thereof may achieve at least one therapeutic outcome selected from the group consisting of a reduction in RBS of ≥ 1, or a reduction from baseline in complete Mayo score of ≥ 3 points and ≥ 30% with an absolute RBS of 0 or 1 within 52 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; a histological improvement within 52 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; a stool frequency subscore of ≤ 1 within 52 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; an RBS of 0 within 52 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; an endoscopic subscore of ≤ 1 within 52 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; a change from baseline in IBDQ score within 52 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof; and combinations thereof.

[0403] In some embodiments, where the patient is administered upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, for at least 52 weeks, the patient was taking corticosteroids at baseline but discontinued corticosteroid use during treatment with the JAK1 inhibitor, the treatment outcome is clinical remission within 52 weeks after initiation of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; endoscopic remission within 52 weeks after initiation of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; complete Mayo score ≦2 with no subscore >1 within 52 weeks after initiation of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof; a reduction from baseline in partial Mayo score over time of ≥ 2 points and a reduction from baseline of ≥ 30% from baseline, plus a reduction in RBS of ≥ 1 or absolute RBS ≤ 1, within 52 weeks of initiating upadacitinib or a pharmaceutically acceptable salt or solid form thereof; a reduction from baseline in RBS of ≥ 1, or a reduction from baseline in complete Mayo score of ≥ 3 points and ≥ 30% with an absolute RBS of 0 or 1, within 52 weeks of initiating upadacitinib or a pharmaceutically acceptable salt or solid form thereof; endoscopic improvement within 52 weeks of initiating upadacitinib or a pharmaceutically acceptable salt or solid form thereof; and combinations thereof.

[0404] In one embodiment of the disclosed methods, the patient is assessed during or at the end of the induction phase for a treatment outcome selected from the group consisting of clinical remission, a complete Mayo score of ≦2 with no subscore >1, endoscopic improvement, endoscopic remission, clinical response, a reduction in RBS of ≧1, or a reduction from baseline in the complete Mayo score of ≧3 points and ≧30% with an absolute RBS of 0 or 1, a reduction from baseline in the partial Mayo score over time of ≧2 points and ≧30% from baseline, as well as a reduction in RBS of ≧1 or absolute RBS ≦1, SF subscore, rectal bleeding subscore, endoscopic subscore, histological improvement, fecal calprotectin level, hs-CRP, IBDQ score, and combinations thereof. In one embodiment of the disclosed methods, the patient is assessed for clinical remission during or at the end of the induction phase. In one embodiment of the disclosed methods, the patient is assessed for endoscopic improvement during or at the end of the induction phase. In one embodiment of the disclosed method, the patient is assessed for achieving a full Mayo score of ≦2 with no subscores >1 during or at the end of the induction phase. In one embodiment of the disclosed method, the patient is assessed for endoscopic remission during or at the end of the induction phase. In one embodiment of the disclosed method, the patient is assessed for clinical response during or at the end of the induction phase. In one embodiment of the disclosed method, the patient is assessed for a partial Mayo score reduction from baseline of ≧2 points and a reduction from baseline of ≧30% over time, as well as a reduction in RBS of ≧1 or an absolute RBS of ≦1 during or at the end of the induction phase. In one embodiment of the disclosed method, the patient is assessed for a change from baseline in full Mayo score during or at the end of the induction phase. In one embodiment of the disclosed method, the patient is assessed for histological improvement during or at the end of the induction phase. In one embodiment, the induction phase is 2 weeks. In one embodiment, the induction phase is 8 weeks. In one embodiment, the induction phase is 12 weeks.

[0405] In one embodiment of the methods of the present disclosure, the patient is assessed during or at the end of the maintenance phase for a treatment outcome selected from the group consisting of endoscopic improvement, achievement of a complete Mayo score < 2 with no subscores > 1, discontinuation of corticosteroid use and clinical remission according to an adapted Mayo score, maintenance of clinical remission in subjects who achieved clinical remission during the induction phase, endoscopic improvement in subjects who achieved clinical remission during the induction phase, clinical response, endoscopic remission, histologic improvement, and combinations thereof.

[0406] In one embodiment of the disclosed method, the patient is assessed for treatment outcome 44 weeks corticosteroid-free after discontinuation of corticosteroids. In one embodiment of the disclosed method, the patient is assessed for treatment outcome by achieving clinical remission 4 weeks after initial administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the disclosed method, the patient is assessed for treatment outcome by achieving clinical remission 8 weeks after initial administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the disclosed method, the patient is assessed for treatment outcome by achieving clinical remission 12 weeks after initial administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the disclosed method, the patient is assessed for treatment outcome by achieving a complete Mayo score of ≦2 with no subscores >1 within 52 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by achieving clinical remission, defined as a stool frequency subscore of ≦1, a rectal bleeding subscore of 0, and an endoscopic subscore with no fragility present of ≦1, within 52 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by achieving an SF subscore of 0, an RBS of 0, and an endoscopic subscore of 0. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by achieving a reduction from baseline in partial Mayo score over time of ≧2 points and a reduction from baseline of ≧30% as well as an RBS reduction of ≧1 or an absolute RBS ≦1, within 2 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof.In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by achieving a reduction from baseline in the partial Mayo score over time of ≥ 2 points and a reduction from baseline of ≥ 30% from baseline, as well as a reduction in RBS of ≥ 1 or an absolute RBS ≤ 1, within 4 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by achieving a reduction from baseline in the partial Mayo score over time of ≥ 2 points and a reduction from baseline of ≥ 30% from baseline, as well as a reduction in RBS of ≥ 1 or an absolute RBS ≤ 1, within 12 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by achieving a clinical response, or a reduction from baseline in the RBS of ≥ 1, or a reduction from baseline in the complete Mayo score of ≥ 3 points and ≥ 30% with an absolute RBS of 0 or 1. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by achieving a reduction from baseline in the partial Mayo score over time of ≥ 2 points and a reduction from baseline of ≥ 30% from baseline, as well as a reduction in RBS of ≥ 1 or an absolute RBS of ≤ 1, within 2 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by achieving a clinical response, or a reduction from baseline in the RBS of ≥ 1, or a reduction from baseline in the complete Mayo score of ≥ 3 points and ≥ 30% with an absolute RBS of 0 or 1. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by achieving a reduction from baseline in the partial Mayo score over time of ≥ 2 points and a reduction from baseline of ≥ 30% from baseline, as well as a reduction in RBS of ≥ 1 or an absolute RBS of ≤ 1, within 4 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the disclosed methods, patients are assessed for treatment outcome by achieving a clinical response, or a reduction in RBS of ≧1, or a reduction from baseline in complete Mayo score of ≧3 points and ≧30% with an absolute RBS of 0 or 1.In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by achieving a reduction from baseline in the partial Mayo score over time of ≥ 2 points and a reduction from baseline of ≥ 30% in addition to a reduction in RBS of ≥ 1 or an absolute RBS of ≤ 1 within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by achieving a stool frequency subscore of ≤ 1 within 2 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by achieving a stool frequency subscore of ≤ 1 within 4 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by achieving a stool frequency subscore of ≤ 1 within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the disclosed methods, the patient is assessed for treatment outcome by achieving a rectal bleeding subscore of 0 over time. In one embodiment of the disclosed methods, the patient is assessed for treatment outcome by achieving an endoscopic subscore of ≦1 within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the disclosed methods, the patient is assessed for treatment outcome by achieving endoscopic improvement within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the disclosed methods, the patient is assessed for treatment outcome by achieving a fecal calprotectin level of less than 150 mg / kg within 4 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the disclosed methods, the patient is assessed for treatment outcome by achieving a fecal calprotectin level of less than 150 mg / kg within 8 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.In one embodiment of the methods of the disclosure, the patient is assessed for therapeutic outcome by achieving fecal calprotectin of less than 150 mg / kg within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for therapeutic outcome by achieving an IBDQ response (an increase in IBDQ from baseline of ≥ 16) within 2 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for therapeutic outcome by achieving an IBDQ response (an increase in IBDQ from baseline of ≥ 16) within 8 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for therapeutic outcome by achieving an IBDQ response (an increase in IBDQ from baseline of ≥ 16) within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the disclosed methods, the patient is assessed for treatment outcome by achieving a change from baseline in hs-CRP within two weeks after initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the disclosed methods, the patient is assessed for treatment outcome by achieving a change from baseline in hs-CRP within eight weeks after initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the disclosed methods, the patient is assessed for treatment outcome by achieving a change from baseline in hs-CRP within 12 weeks after initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the disclosed methods, the patient is assessed for treatment outcome by achieving a change from baseline in fecal calprotectin within eight weeks after initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by achieving a change from baseline in fecal calprotectin within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by achieving a change in corticosteroid dose within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by a change from baseline in adapted Mayo score, complete Mayo score, partial Mayo score, and / or Mayo subscore within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by a change from baseline in UCEIS score within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by achieving histologic response (defined as a Geboes score <2) within 8 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by achieving histologic response (defined as a Geboes score <2) within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by change from baseline in histologic score within 8 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by change from baseline in histologic score within 8 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof.In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by changes from baseline in laboratory and nutritional parameters (e.g., hemoglobin, hematocrit, albumin, total protein concentration, and body weight) within 8 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by changes from baseline in laboratory and nutritional parameters (e.g., hemoglobin, hematocrit, albumin, total protein concentration, and body weight) within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by changes from baseline in subject-recorded stool frequency (absolute value) within 8 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by the change from baseline in subject-recorded stool frequency (absolute value) within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by the change from baseline in subject-recorded stool frequency (absolute value) within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by change from baseline in IBDQ score within 8 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by change from baseline in IBDQ score within 12 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by change from baseline in EQ-5D-5L score within 8 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by change from baseline in EQ-5D-5L score within 12 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by the change from baseline in WPAI:UC score within 8 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by the change from baseline in WPAI:UC score within 12 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by the change in SF-36, PCT, MCS components, and domain scores within 8 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by the change in SF-36, PCT, MCS components, and domain scores within 12 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the disclosed methods, the patient is assessed for treatment outcome by change in PGIC score within 8 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the disclosed methods, the patient is assessed for treatment outcome by change in PGIC score within 12 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof.In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by the change from baseline in FACIT-F score within 8 weeks after initial administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by the change from baseline in FACIT-F score within 12 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by the change from baseline in UC-SQ score within 8 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment of the methods of the disclosure, the patient is assessed for treatment outcome by the change from baseline in UC-SQ score within 8 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the patient is administered at least 14 doses, 28 doses, or at least 42 doses, or at least 56 doses of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, during the induction phase.

[0407] In one aspect, certain therapeutic results are maintained by the patient during the maintenance phase. The maintenance phase can be continued indefinitely. In one embodiment, the maintenance phase is at least 36 weeks, including at least 37 weeks, at least 38 weeks, at least 39 weeks, at least 40 weeks, at least 41 weeks, at least 42 weeks, at least 43 weeks, at least 44 weeks, at least 45 weeks, at least 46 weeks, at least 47 weeks, or at least 48 weeks after the patient achieves clinical remission or clinical response. In one embodiment, the maintenance phase is at least an additional 40 weeks. In one embodiment, the maintenance phase is at least an additional 44 weeks after the patient achieves clinical remission or clinical response. In one embodiment, the treatment outcome maintained by the patient during the maintenance phase is selected from the group consisting of clinical remission, a complete Mayo score of ≦2 with no subscore >1, endoscopic remission, clinical response, a partial Mayo score reduction of ≧2 points from baseline and ≧30% reduction from baseline, as well as a complete Mayo score reduction of ≧1 or absolute RBS ≦1, a reduction of ≧1 RBS, or a reduction of ≧3 points and ≧30% from baseline with an absolute RBS of 0 or 1, endoscopic improvement, and combinations thereof. In one embodiment, the treatment outcome maintained by the patient during the maintenance phase is endoscopic remission. In one embodiment, the treatment outcome maintained by the patient during the maintenance phase is endoscopic response. In one embodiment, the treatment outcome maintained by the patient during the maintenance phase is clinical remission. In one embodiment, the treatment outcome maintained by the patient during the maintenance phase is corticosteroid-free remission.

[0408] In one embodiment of the disclosed method, the patient is evaluated for clinical remission during the maintenance phase. In one embodiment, the patient is evaluated for endoscopic improvement during the maintenance phase. In one embodiment, the patient is evaluated for clinical remission, a complete Mayo score of ≦2 with no subscores >1 during the maintenance phase. In one embodiment of the disclosed method, the patient is evaluated for endoscopic remission during the maintenance phase. In one embodiment of the disclosed method, the patient is evaluated for clinical response during the maintenance phase, or a partial Mayo score reduction of ≧2 points from baseline and a reduction of ≧30% from baseline, plus a reduction in RBS of ≧1 or an absolute RBS of ≦1, or a reduction in RBS of ≧1, or a reduction in complete Mayo score of ≧3 points and ≧30% from baseline with an absolute RBS of 0 or 1.

[0409] In one embodiment, the disclosure provides a method for treating an inflammatory disease, in one aspect, for treating ulcerative colitis, comprising: (a) administering to a patient a dose of a JAK1 inhibitor (e.g., upadacitinib or a pharmaceutically acceptable salt or solid form thereof) at week 0 and once daily (QD) thereafter for 8 weeks, wherein the dose is 45 mg QD. In one embodiment, the method further comprises: (b) administering to the patient an additional dose once daily thereafter for at least 44 additional weeks, wherein the dose is 15 mg or 30 mg QD. In one embodiment, the dose is administered orally.

[0410] In one embodiment, 8 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, patients are assessed for clinical remission and / or a complete Mayo score <2 with no subscores >1. In one embodiment, 8 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, patients are assessed for clinical response and / or a partial Mayo score reduction of ≥2 points from baseline and a reduction of ≥30% from baseline, as well as a reduction in RBS of ≥1 or absolute RBS <1, and / or a reduction in RBS of ≥1, or a complete Mayo score reduction of ≥3 points and ≥30% from baseline with an absolute RBS of 0 or 1, and / or endoscopic improvement and / or endoscopic remission. In one embodiment, 6 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, patients are assessed for clinical remission and / or a complete Mayo score <2 with no subscores >1, and / or endoscopic remission. In one embodiment, 6 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, patients are assessed for a reduction in RBS of ≥ 1, or a reduction from baseline in complete Mayo score of ≥ 3 points and ≥ 30% with an absolute RBS of 0 or 1, and / or clinical response, and / or a reduction from baseline in partial Mayo score of ≥ 2 points and a reduction from baseline of ≥ 30% from baseline, as well as a reduction in RBS of ≥ 1 or absolute RBS ≤ 1, and / or endoscopic improvement. In one embodiment, 4 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, patients are assessed for clinical remission, and / or a complete Mayo score ≤ 2 with no subscores > 1, and / or endoscopic remission. In one embodiment, 4 weeks after initiation of administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, patients are assessed for a reduction in RBS of ≥ 1, or a reduction from baseline in complete Mayo score of ≥ 3 points and ≥ 30% with an absolute RBS of 0 or 1, and / or clinical response, and / or a reduction from baseline in partial Mayo score of ≥ 2 points and a reduction from baseline of ≥ 30% from baseline, as well as a reduction in RBS of ≥ 1 or absolute RBS ≤ 1, and / or endoscopic improvement.In one embodiment, two weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, patients are assessed for clinical remission, and / or a complete Mayo score <2 with no subscores >1, and / or endoscopic remission. In one embodiment, two weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, patients are assessed for a complete Mayo score reduction of ≥1 by RBS, or a reduction of ≥3 points and ≥30% from baseline with an absolute RBS of 0 or 1, and / or clinical response, and / or a partial Mayo score reduction of ≥2 points from baseline and a reduction of ≥30% from baseline with an RBS reduction of ≥1 or absolute RBS <1, and / or endoscopic improvement.

[0411] In one embodiment, 48 weeks after initiation of upadacitinib or a pharmaceutically acceptable salt or solid form thereof, patients are assessed for clinical remission according to the adapted Mayo score over time (defined as an SFS≦1, an RBS of 0, and an endoscopic subscore≦1), clinical remission according to the complete Mayo score (complete Mayo score≦2 without subscores >1), clinical remission according to the partial Mayo score (defined as a partial Mayo score≦2 without subscores >1), a stool frequency subscore≦1, an RBS of 0, and an endoscopic subscore≦1 with no frailty present, and clinical response according to the adapted Mayo score (defined as an adapted Mayo score reduction from BL of ≧2 points and a reduction from BL of ≧30% plus a reduction in RBS of ≧1).

[0412] In one embodiment, the disclosure provides a method for treating ulcerative colitis, comprising: (a) administering a dose of a JAK1 inhibitor (e.g., upadacitinib or a pharmaceutically acceptable salt or solid form thereof) via oral route to a patient at week 0 and once daily thereafter, wherein the dose of the JAK1 inhibitor comprises 15 mg, 30 mg, or 45 mg QD, or any combination thereof.

[0413] In one embodiment, the disclosure provides a method for treating ulcerative colitis, comprising administering 15 mg to 45 mg of a JAK1 inhibitor to a patient. In one embodiment, the disclosure provides a method for treating ulcerative colitis, comprising orally administering 15 mg of a JAK1 inhibitor QD to a patient. In one embodiment, the disclosure provides a method for treating ulcerative colitis, comprising orally administering 30 mg of a JAK1 inhibitor QD to a patient. In one embodiment, the disclosure provides a method for treating ulcerative colitis, comprising orally administering 45 mg of a JAK1 inhibitor QD to a patient. In any such embodiment, the JAK1 inhibitor can be upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In any such embodiment, the JAK1 inhibitor can be in a once-daily modified-release formulation. In any such embodiment, the patient can have moderate to severe active ulcerative colitis prior to treatment.

[0414] In one embodiment, administration of a JAK1 inhibitor according to the present disclosure is further described in the Examples herein below or in FIG.

[0415] In one embodiment, the disclosure provides a method for treating ulcerative colitis, comprising: a) administering to a patient at least one induction dose of a JAK1 inhibitor (e.g., upadacitinib or a pharmaceutically acceptable salt or solid form thereof), wherein the induction dose comprises 15 mg to 45 mg of the JAK1 inhibitor. In one aspect, the induction dose comprises 15 mg, 30 mg, or 45 mg. In one aspect, the induction dose comprises 45 mg. In one aspect, the induction dose is administered orally. In one aspect, the induction dose is administered QD. In one aspect, the induction dose is administered for 8 weeks. In one aspect, the induction dose is administered for 6 weeks. In one aspect, the induction dose is administered for 4 weeks. In one embodiment, the induction dose is administered for up to 12 weeks, including 2 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, or 12 weeks.

[0416] In one embodiment, the induction dose comprises 45 mg of a JAK1 inhibitor administered QD.

[0417] In one embodiment, the induction dose comprises 30 mg of a JAK1 inhibitor administered QD.

[0418] In one embodiment, the induction dose comprises 15 mg of a JAK1 inhibitor administered QD.

[0419] In one embodiment, the JAK1 inhibitor is upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0420] In one embodiment, the loading dose is in a once-daily modified release formulation.

[0421] In one embodiment, the method further comprises: b) administering to the patient a first maintenance dose of a JAK1 inhibitor (e.g., upadacitinib or a pharmaceutically acceptable salt or solid form thereof) after the final induction dose has been administered; and c) thereafter administering to the patient at least one additional maintenance dose once daily.

[0422] In one embodiment, the first maintenance dose comprises 15 mg to 30 mg of the JAK1 inhibitor. In one aspect, the first maintenance dose comprises 15 mg or 30 mg of the JAK1 inhibitor. In one aspect, the first maintenance dose is less than the induction dose. In one aspect, the first maintenance dose is administered QD. In one aspect, the first maintenance dose is 15 mg. In one aspect, the first maintenance dose is 30 mg. In one aspect, the first maintenance dose is administered orally. In one aspect, the first maintenance dose is a once-daily dose in a modified release formulation.

[0423] In one aspect, the at least one additional maintenance dose comprises 15 mg to 30 mg of the JAK1 inhibitor. In one aspect, the at least one additional maintenance dose comprises 15 mg or 30 mg. In one aspect, the at least one additional maintenance dose is administered orally. In one aspect, the at least one additional maintenance dose is administered QD. In one embodiment, the at least one additional maintenance dose comprises 15 mg of the JAK1 inhibitor administered QD. In one embodiment, the at least one additional maintenance dose comprises 30 mg of the JAK1 inhibitor administered QD. In one aspect, the at least one additional maintenance dose is in a once-daily modified-release formulation.

[0424] In any of the above-described embodiments, the JAK1 inhibitor can be upadacitinib or a pharmaceutically acceptable salt or solid form thereof.

[0425] In one aspect of any of the above-described embodiments, the patient is one who has had an inadequate response, or has experienced loss of response or intolerance to prior treatment with conventional treatments (e.g., aminosalicylates, corticosteroids, immunosuppressants) or biologic agents. In one aspect of any of the above-described embodiments, the patient is one who has had an inadequate response, has experienced loss of response, or has experienced intolerance to prior treatment with an anti-TNF agent.

[0426] In one aspect of any of the above embodiments, the patient has not been pre-treated with an aminosalicylate, a corticosteroid, an immunosuppressant, a biologic agent, or an anti-TNF agent.

[0427] In one aspect of any of the above embodiments, the patient had moderate to severe active ulcerative colitis prior to administration of the treatment or induction dose.

[0428] In one embodiment, the disclosure further provides a method for inducing clinical remission of ulcerative colitis in a patient, or a complete Mayo score <2 with no subscores >1, comprising: a) administering to the patient at least one induction dose of a JAK1 inhibitor (e.g., upadacitinib or a pharmaceutically acceptable salt or solid form thereof) as described above or herein. In one embodiment, the induction dose comprises 30 mg to 45 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the induction dose is administered at week 0 and once daily (QD) thereafter for up to 12 weeks (e.g., 4, 5, 6, 7, or 8, or 9, or 10, or 11, or 12 weeks), wherein the dose is 30 mg QD or 45 mg QD. In one embodiment, the method further comprises maintaining clinical remission of ulcerative colitis, or a complete Mayo score of ≦2 with no subscores >1, the method further comprising: b) administering a first maintenance dose of the JAK1 inhibitor to the patient after the final induction dose is administered; and c) subsequently administering at least one additional maintenance dose to the patient as described above or herein. In one embodiment, the at least one additional maintenance dose is administered once daily. In one embodiment, the additional maintenance dose is administered once daily for at least 36 additional weeks, including at least 36 weeks, at least 37 weeks, at least 38 weeks, at least 39 weeks, at least 40 weeks, at least 41 weeks, at least 42 weeks, at least 43 weeks, at least 44 weeks, at least 56 weeks, at least 112 weeks, at least 308 weeks, or at least 420 weeks. In one embodiment, the additional maintenance dose is administered once daily for at least 44 additional weeks. In one embodiment, the maintenance dose is 15 mg or 30 mg QD. In one embodiment, the induction dose and maintenance dose are administered orally. In one embodiment, the patient has active ulcerative colitis with a matched Mayo score of 5 to 9 points and an endoscopy subscore of 2 or 3 prior to administration of the first induction dose. In one embodiment, the patient has moderate to severe active ulcerative colitis prior to administration of the first induction dose.In one embodiment, the patient has had an inadequate response to or experienced intolerance to prior treatment with conventional treatments (e.g., aminosalicylates, corticosteroids, immunosuppressants), or biologic agents and / or anti-TNF agents. In one embodiment, the patient has not received prior treatment with aminosalicylates, corticosteroids, immunosuppressants, biologic agents and / or anti-TNF agents. In one embodiment, clinical remission, or a complete Mayo score of ≦2 with no subscores >1, is achieved within 4 weeks or 8 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, clinical remission, or a complete Mayo score of ≦2 with no subscores >1, is achieved within 12 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, clinical remission, or a complete Mayo score of ≦2 with no subscores >1, is achieved within 10 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, clinical remission, or a complete Mayo score of ≦2 with no subscores >1, is achieved within 8 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the patient achieves a stool frequency subscore of ≦1, an RBS of 0, and an endoscopic subscore of ≦1 prior to administration of the first maintenance dose. In one embodiment, the patient achieves a complete Mayo score of ≦2 with no subscores >1 prior to administration of the first maintenance dose. In one embodiment, the induction dose and maintenance doses are in a once-daily modified-release formulation.

[0429] In one embodiment, the disclosure provides a method for inducing endoscopic remission of ulcerative colitis, comprising: (a) administering to a patient at least one induction dose of a JAK1 inhibitor (e.g., upadacitinib or a pharmaceutically acceptable salt or solid form thereof), wherein the induction dose comprises 30-45 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the induction dose is administered at week 0 and once daily (QD) thereafter for up to 12 weeks (e.g., 4, 5, 6, 7, or 8, or 9, or 10, or 11, or 12 weeks), and the dose is 30 mg QD or 45 mg QD. In one embodiment, the method further comprises maintaining endoscopic remission of ulcerative colitis, the method further comprising (b) administering a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt or solid form thereof to the patient after the final induction dose has been administered, and (c) subsequently administering at least one additional maintenance dose as described above or herein. In one embodiment, the at least one additional maintenance dose is administered once daily. In one embodiment, the additional maintenance dose is administered once daily for at least an additional 36 weeks, including at least 36 weeks, at least 37 weeks, at least 38 weeks, at least 39 weeks, at least 40 weeks, at least 41 weeks, at least 42 weeks, at least 43 weeks, at least 44 weeks, at least 56 weeks, at least 112 weeks, at least 308 weeks, or at least 420 weeks. In one embodiment, the additional maintenance dose is administered once daily for at least an additional 44 weeks. In one embodiment, the maintenance dose is 15 mg or 30 mg QD. In one embodiment, the induction dose and maintenance dose are administered orally. In one embodiment, the patient has active ulcerative colitis with a matched Mayo score of 5 to 9 points and an endoscopy subscore of 2 or 3 prior to administration of the first induction dose. In one embodiment, the patient has moderate to severe active ulcerative colitis prior to administration of the first induction dose.In one embodiment, the patient has had an inadequate response to or experienced intolerance to prior treatment with conventional treatments (e.g., aminosalicylates, corticosteroids, immunosuppressants), or biologic and / or anti-TNF agents. In one embodiment, the patient has not received prior treatment with aminosalicylates, corticosteroids, immunosuppressants, anti-TNF agents, and / or biologic agents. In one embodiment, endoscopic remission is achieved within 4 weeks or 8 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, endoscopic remission is achieved within 12 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, endoscopic remission is achieved within 10 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, endoscopic remission is achieved within 8 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the patient achieves an endoscopic subscore of 0 prior to administration of the first maintenance dose. In one embodiment, the induction dose and maintenance doses are in a once-daily modified release formulation.

[0430] In one embodiment, the disclosure further provides a method for inducing a clinical response in ulcerative colitis in a patient, or inducing a reduction from baseline in the complete Mayo score of ≧3 points and ≧30% with an RBS reduction of ≧1 or an absolute RBS of 0 or 1, or inducing a reduction from baseline in the partial Mayo score of ≧2 points and ≧30% with an RBS reduction of ≧1 or an absolute rectal bleeding subscore ≦1, comprising: a) administering to the patient at least one induction dose of a JAK1 inhibitor (e.g., upadacitinib or a pharmaceutically acceptable salt or solid form thereof) as described above or herein. In one embodiment, the induction dose comprises 30 mg to 45 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the induction dose is administered at week 0 and once daily (QD) thereafter for up to 8 weeks (e.g., 4, 5, 6, 7, or 8 weeks), and the dose is 30 mg QD or 45 mg QD. In one embodiment, the method further comprises maintaining a clinical response in ulcerative colitis, or maintaining a complete Mayo score reduction from baseline of ≥3 points and ≥30% with an RBS reduction of ≥1 or an absolute RBS of 0 or 1, or maintaining a partial Mayo score reduction from baseline of ≥2 points and ≥30% with an RBS reduction of ≥1 or an absolute rectal bleeding subscore ≤1, the method further comprising b) administering to the patient a first maintenance dose of the JAK1 inhibitor after the final induction dose is administered, and c) thereafter administering to the patient at least one additional maintenance dose as described above or herein. In one embodiment, the at least one additional maintenance dose is administered once daily. In one embodiment, the additional maintenance dose is administered once daily for at least an additional 36 weeks, including at least 36 weeks, at least 37 weeks, at least 38 weeks, at least 39 weeks, at least 40 weeks, at least 41 weeks, at least 42 weeks, at least 43 weeks, at least 44 weeks, at least 56 weeks, at least 112 weeks, at least 308 weeks, or at least 420 weeks. In one embodiment, the additional maintenance dose is administered once daily for at least an additional 44 weeks.In one embodiment, the maintenance dose is 15 mg or 30 mg QD. In one embodiment, the induction dose and maintenance dose are administered orally. In one embodiment, the patient has active ulcerative colitis with a matched Mayo score of 5 to 9 points and an endoscopy subscore of 2 or 3 prior to administration of the first induction dose. In one embodiment, the patient has moderate to severe active ulcerative colitis prior to administration of the first induction dose. In one embodiment, the patient has had an inadequate response to or experienced intolerance to prior treatment with conventional treatments (e.g., aminosalicylates, corticosteroids, immunosuppressants), or biologic agents and / or anti-TNF agents. In one embodiment, the patient has not received prior treatment with aminosalicylates, corticosteroids, immunosuppressants, biologic agents and / or anti-TNF agents. In one embodiment, the clinical response, or a reduction from baseline in the complete Mayo score of ≧3 points and ≧30% with an RBS reduction of ≧1 or an absolute RBS of 0 or 1, or a reduction from baseline in the partial Mayo score of ≧2 points and ≧30% with an RBS reduction of ≧1 or an absolute rectal bleeding subscore ≦1, is achieved within 4 weeks or 8 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the clinical response, or a reduction from baseline in the complete Mayo score of ≧3 points and ≧30% with an RBS reduction of ≧1 or an absolute RBS of 0 or 1, is achieved within 12 weeks of initiating administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, a clinical response, or a reduction from baseline in the complete Mayo score of ≧3 points and ≧30% with an RBS reduction of ≧1 or an absolute RBS of 0 or 1, or a reduction from baseline in the partial Mayo score of ≧2 points and ≧30% with an RBS reduction of ≧1 or an absolute rectal bleeding subscore ≦1, is achieved within 10 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof.In one embodiment, the clinical response, or a reduction from baseline in the complete Mayo score of ≥ 3 points and ≥ 30% with an RBS reduction of ≥ 1 or an absolute RBS of 0 or 1, or a reduction from baseline in the partial Mayo score of ≥ 2 points and ≥ 30% with an RBS reduction of ≥ 1 or an absolute rectal bleeding subscore ≤ 1, is achieved within 8 weeks of initiating administration of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the patient achieves a reduction from baseline in the adapted Mayo score of ≥ 2 points and ≥ 30% with an RBS reduction of ≥ 1 or an absolute rectal bleeding subscore of 0 or 1 prior to administration of the first maintenance dose. In one embodiment, the patient achieves a reduction from baseline in the partial Mayo score of ≥ 2 points and ≥ 30% with an RBS reduction of ≥ 1 or an absolute rectal bleeding subscore ≤ 1 prior to administration of the first maintenance dose. In one embodiment, the patient achieves, prior to administration of the first maintenance dose, a reduction from baseline in RBS of ≥ 1, or a reduction from baseline in complete Mayo score of ≥ 3 points and ≥ 30%, accompanied by an absolute rectal bleeding subscore of 0 or 1. In one embodiment, the induction dose and maintenance doses are in a once-daily modified-release formulation.

[0431] In one embodiment, the disclosure further provides a method for inducing endoscopic improvement of ulcerative colitis in a patient, the method comprising: a) administering to the patient at least one induction dose of a JAK1 inhibitor (e.g., upadacitinib or a pharmaceutically acceptable salt or solid form thereof), as described above or herein. In one embodiment, the induction dose comprises 30-45 mg of upadacitinib or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the induction dose is administered at week 0 and once daily (QD) thereafter for up to 12 weeks (e.g., 4, 5, 6, 7, 8, 9, 10, 11, or 12 weeks), and the dose is 30 mg QD or 45 mg QD. In one embodiment, the method further comprises maintaining endoscopic improvement of the ulcerative colitis, the method further comprising: b) administering a first maintenance dose of the JAK1 inhibitor to the patient after the final induction dose has been administered; and c) subsequently administering at least one additional maintenance dose to the patient as described above or herein. In one embodiment, the at least one additional maintenance dose is administered once daily. In one embodiment, the additional maintenance dose is administered once daily for at least 36 additional weeks, including at least 36 weeks, at least 37 weeks, at least 38 weeks, at least 39 weeks, at least 40 weeks, at least 41 weeks, at least 42 weeks, at least 43 weeks, at least 44 weeks, at least 56 weeks, at least 112 weeks, at least 308 weeks, or at least 420 weeks. In one embodiment, the additional maintenance dose is administered once daily for at least 44 additional weeks. In one embodiment, the maintenance dose is 15 mg or 30 mg QD. In one embodiment, the induction dose and the maintenance dose are administered orally. In one embodiment, the patient has active ulcerative colitis prior to administration of the first induction dose, with a matched Mayo score of 5 to 9 points and an endoscopy subscore of 2 or 3. In one embodiment, the patient has moderate to severe active ulcerative colitis prior to administration of the first induction dose.In one embodiment, the patient has had an inadequate response to or experienced intolerance to conventional treatments (e.g., aminosalicylates, corticosteroids, and immunosuppressants), or prior treatment with biologic agents and / or anti-TNF agents. In one embodiment, the patient has not received prior treatment with aminosalicylates, corticosteroids, immunosuppressants, biologic agents, and / or anti-TNF agents. In one embodiment, endoscopic improvement is achieved within 8 weeks or within 16 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, endoscopic improvement is achieved within 12 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, endoscopic improvement is achieved within 10 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, endoscopic improvement is achieved within 8 weeks after initiation of administration of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof. In one embodiment, the patient achieves an endoscopic subscore of < 1 prior to administration of the first maintenance dose. In one embodiment, the induction dose and maintenance doses are in a once-daily modified release formulation.

[0432] In one embodiment, the disclosure further provides a method of maintaining clinical remission or maintaining a complete Mayo score of ≦2 without an ulcerative colitis subscore >1 in a patient, comprising administering 15 mg or 30 mg of upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, to the patient. In one embodiment, upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, is administered once daily for at least 36 weeks, including at least 37 weeks, at least 38 weeks, at least 39 weeks, at least 40 weeks, at least 41 weeks, at least 42 weeks, at least 43 weeks, or at least 44 weeks. In one embodiment, upadacitinib, or a pharmaceutically acceptable salt or solid form thereof, is administered orally. In one embodiment, the patient has had an inadequate response to, or experienced intolerance to, conventional treatments (e.g., aminosalicylates, corticosteroids, immunosuppressants), or prior treatment with a biologic ...

Claims

1. 1. A method of inducing clinical remission of Crohn's disease in a patient, comprising: a. administering orally to a patient once daily for at least 4 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. The method wherein the patient achieves clinical remission within 12 weeks after administration of the first induction dose.

2. 2. The method of claim 1, wherein clinical remission of Crohn's disease is induced within 4 weeks after administration of the first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

3. 1. A method of inducing a clinical response in Crohn's disease in a patient, comprising: a. administering orally to a patient once daily for at least two weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. The method wherein the patient achieves a clinical response.

4. 4. The method of claim 3, wherein a clinical response in Crohn's disease is induced within 4 weeks after administration of the first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

5. 4. The method of claim 3, wherein a clinical response in Crohn's disease is induced within 12 weeks after administration of the first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

6. 1. A method of inducing endoscopic remission of Crohn's disease in a patient, comprising: a. administering orally to a patient once daily for at least 12 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. A method wherein the patient achieves endoscopic remission within 12 weeks after administration of the first induction dose.

7. 1. A method of inducing an endoscopic response in Crohn's disease in a patient, comprising: a. administering orally to a patient once daily for at least 4 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; method.

8. 8. The method of claim 7, wherein an endoscopic response for Crohn's disease is induced within 12 weeks after administration of the first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

9. 1. A method of inducing corticosteroid-free remission of Crohn's disease in a patient, comprising: a. administering orally to a patient once daily for at least 12 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. A method wherein the patient achieves steroid-free remission within 12 weeks after administration of the first induction dose.

10. The method of any one of claims 1 to 9, wherein the patient is an adult with moderate to severe active Crohn's disease.

11. 11. The method of any of claims 1-10, wherein the patient experiences a reduction in CDAI of more than 150 within 12 weeks after administration of the first induction dose.

12. The method of any of claims 1 to 10, wherein the patient has had an inadequate response to or experienced intolerance to prior treatment with a corticosteroid, immunosuppressant or biologic agent.

13. 13. The method of claim 12, wherein the patient had an inadequate response to or experienced intolerance to pretreatment with an anti-TNF agent.

14. 14. The method of claim 13, wherein the anti-TNF agent is infliximab, adalimumab, or certolizumab pegol.

15. 11. The method of claim 10, wherein the patient has had a diagnosis of Crohn's disease for more than 10 years, has had an inadequate response to, or has experienced intolerance to, one or more prior treatments.

16. 16. The method of claim 15, wherein the pretreatment is selected from the group consisting of corticosteroids, immunosuppressants, antibiotics, and biological therapies.

17. 1. A method of inducing and maintaining clinical remission of Crohn's disease in a patient, comprising: a. administering orally to a patient once daily for at least 4 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. the patient achieves clinical remission within 4 weeks after administration of the first induction dose; c. After the final induction dose has been administered, administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof orally once daily, comprising 30 mg of upadacitinib or a 30 mg free base equivalent of a pharmaceutically acceptable salt thereof; d. administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; e. The method wherein the patient maintains clinical remission 52 weeks after administration of the first induction dose.

18. 1. A method of inducing and maintaining a clinical response in Crohn's disease in a patient, comprising: a. administering orally to a patient once daily for at least two weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. the patient achieves a clinical response within 2 weeks after administration of the first induction dose; c. After the final induction dose has been administered, administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof orally once daily, comprising 30 mg of upadacitinib or a 30 mg free base equivalent of a pharmaceutically acceptable salt thereof; d. administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; e. The method wherein the patient maintains the clinical response 52 weeks after administration of the first induction dose.

19. 19. The method of claim 18, wherein a clinical response in Crohn's disease is induced within 4 weeks after administration of the first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

20. 20. The method of claim 19, wherein a clinical response in Crohn's disease is induced within 12 weeks after administration of the first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

21. 1. A method of inducing and maintaining endoscopic remission of Crohn's disease in a patient, comprising: a. administering orally to a patient once daily for at least 4 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. After the final induction dose has been administered, administering orally to the patient once daily a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 30 mg of upadacitinib or 30 mg of the free base equivalent of a pharmaceutically acceptable salt thereof; c. administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; d. The method wherein the patient maintains endoscopic remission 52 weeks after administration of the first induction dose.

22. 22. The method of claim 21, wherein endoscopic remission of Crohn's disease is induced within 12 weeks after administration of the first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

23. 1. A method of inducing and maintaining an endoscopic response in Crohn's disease in a patient, comprising: a. administering orally to a patient once daily for at least 4 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. the patient achieves an endoscopic response within 4 weeks after administration of the first induction dose; c. After the final induction dose has been administered, administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof orally once daily, comprising 30 mg of upadacitinib or a 30 mg free base equivalent of a pharmaceutically acceptable salt thereof; d. administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; e. The method wherein the patient maintains an endoscopic response 52 weeks after administration of the first induction dose.

24. 24. The method of claim 23, wherein the endoscopic response of Crohn's disease is induced within 12 weeks after administration of the first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

25. 1. A method of inducing and maintaining corticosteroid-free remission of Crohn's disease in a patient, comprising: a. administering orally to a patient once daily for at least 12 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. the patient achieves steroid-free remission within 12 weeks after administration of the first induction dose; c. After the final induction dose has been administered, administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof orally once daily, comprising 30 mg of upadacitinib or a 30 mg free base equivalent of a pharmaceutically acceptable salt thereof; d. administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; e. A method wherein the patient remains in corticosteroid-free remission for 52 weeks after administration of the first induction dose.

26. The method of any one of claims 17 to 25, wherein the patient is an adult with moderate to severe active Crohn's disease.

27. 26. The method of any of claims 17-25, wherein the patient experiences a reduction in CDAI of more than 150 within 12 weeks after administration of the first induction dose.

28. The method of any of claims 17 to 25, wherein the patient has had an inadequate response to or experienced intolerance to prior treatment with a corticosteroid, immunosuppressant or biologic agent.

29. 29. The method of claim 28, wherein the patient had an inadequate response to or experienced intolerance to pretreatment with an anti-TNF agent.

30. 30. The method of claim 29, wherein the anti-TNF agent is infliximab, adalimumab, or certolizumab pegol.

31. 27. The method of claim 26, wherein the patient has had a diagnosis of Crohn's disease for more than 10 years, has had an inadequate response to, or has experienced intolerance to, one or more prior treatments.

32. 32. The method of claim 31, wherein the pretreatment is selected from a corticosteroid, an immunosuppressant, an antibiotic, and a biological therapy.

33. 1. A method of inducing and maintaining clinical remission of Crohn's disease in a patient, comprising: a. administering orally to a patient once daily for at least 4 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. the patient achieves clinical remission within 4 weeks after administration of the first induction dose; c. After the final induction dose has been administered, administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof orally once daily, comprising 15 mg of upadacitinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 15 mg of the free base; d. administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; e. The method wherein the patient maintains clinical remission 52 weeks after administration of the first induction dose.

34. 1. A method of inducing and maintaining a clinical response in Crohn's disease in a patient, comprising: a. administering orally to a patient once daily for at least two weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. the patient achieves a clinical response within 2 weeks after administration of the first induction dose; c. After the final induction dose has been administered, administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof orally once daily, comprising 15 mg of upadacitinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 15 mg of the free base; d. administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; e. The method wherein the patient maintains the clinical response 52 weeks after administration of the first induction dose.

35. 35. The method of claim 34, wherein a clinical response in Crohn's disease is induced within 4 weeks after administration of the first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

36. 35. The method of claim 34, wherein a clinical response in Crohn's disease is induced within 12 weeks after administration of the first induction dose of upadacitinib or a pharmaceutically acceptable salt thereof.

37. 1. A method of inducing and maintaining endoscopic remission of Crohn's disease in a patient, comprising: a. administering orally to a patient once daily for at least 4 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. the patient achieves endoscopic remission within 12 weeks after administration of the first induction dose; c. After the final induction dose has been administered, administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof orally once daily, comprising 15 mg of upadacitinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 15 mg of the free base; d. administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; e. The method wherein the patient maintains endoscopic remission 52 weeks after administration of the first induction dose.

38. 1. A method of inducing and maintaining an endoscopic response in Crohn's disease in a patient, comprising: a. administering orally to a patient once daily for at least 4 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. the patient achieves an endoscopic response within 12 weeks after administration of the first induction dose; c. After the final induction dose has been administered, administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof orally once daily, comprising 15 mg of upadacitinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 15 mg of the free base; d. administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; e. The method wherein the patient maintains an endoscopic response 52 weeks after administration of the first induction dose.

39. 1. A method of inducing and maintaining corticosteroid-free remission of Crohn's disease in a patient, comprising: a. administering orally to a patient once daily for at least 12 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or 45 mg of the free base equivalent of a pharmaceutically acceptable salt thereof; b. the patient achieves steroid-free remission within 4 weeks after administration of the first induction dose; c. After the final induction dose has been administered, administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof orally once daily, comprising 15 mg of upadacitinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 15 mg of the free base; d. administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; e. A method wherein the patient remains in corticosteroid-free remission for 52 weeks after administration of the first induction dose.

40. 40. The method of any one of claims 33 to 39, wherein the patient is an adult with moderate to severe active Crohn's disease.

41. 40. The method of any of claims 33-39, wherein the patient experiences a reduction in CDAI of greater than 150 within 12 weeks after administration of the first induction dose.

42. 40. The method of any of claims 33 to 39, wherein the patient has had an inadequate response to or experienced intolerance to prior treatment with a corticosteroid, immunosuppressant or biologic agent.

43. 43. The method of claim 42, wherein the patient had an inadequate response to or experienced intolerance to pretreatment with an anti-TNF agent.

44. 44. The method of claim 43, wherein the anti-TNF agent is infliximab, adalimumab, or certolizumab pegol.

45. 41. The method of claim 40, wherein the patient has had a diagnosis of Crohn's disease for more than 10 years, has had an inadequate response to, or has experienced intolerance to, one or more prior treatments.

46. 46. ​​The method of claim 45, wherein the pretreatment is selected from corticosteroids, immunosuppressants, antibiotics, and biological therapies.

47. 1. A method of inducing clinical remission of ulcerative colitis in a patient, comprising: a. administering orally to a patient once daily for at least 4 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. The method wherein the patient achieves clinical remission within 4 weeks after administration of the first induction dose.

48. 1. A method of inducing clinical remission of ulcerative colitis in a patient, comprising: a. administering orally to a patient once daily for at least 6 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. The method wherein the patient achieves clinical remission within 6 weeks after administration of the first 45 mg induction dose.

49. 1. A method of inducing clinical remission of ulcerative colitis in a patient, comprising: a. administering orally to a patient once daily for at least 8 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. The method wherein the patient achieves clinical remission within 8 weeks after administration of the first 45 mg induction dose.

50. 1. A method of inducing endoscopic improvement of ulcerative colitis in a patient, comprising: a. administering orally to a patient once daily for at least 8 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. A method wherein the patient achieves endoscopic improvement within 8 weeks after administration of the first induction dose.

51. 1. A method of inducing endoscopic remission of ulcerative colitis in a patient, comprising: a. administering orally to a patient once daily for at least 8 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. A method wherein the patient achieves endoscopic remission within 8 weeks after administration of the first 45 mg induction dose.

52. 52. The method of any one of claims 47 to 51, wherein the patient has moderate to severe active ulcerative colitis.

53. 52. The method of any of claims 47-51, wherein the patient is taking a corticosteroid at the time of the first induction dose.

54. 54. The method of claim 53, wherein corticosteroids are not used in clinical remission, endoscopic improvement, or endoscopic remission.

55. 55. The method of any of claims 47 to 54, wherein the patient has shown an inadequate response, loss of response or intolerance to one or more corticosteroids, immunosuppressants or biological treatments.

56. 56. The method of claim 55, wherein the immunosuppressant is selected from oral azathioprine, 6-mercaptopurine, injectable methotrexate, and tacrolimus.

57. 56. The method of claim 55, wherein the biological therapy is selected from infliximab, adalimumab, golimumab, and vedolizumab.

58. 56. The method of claim 55, wherein an inadequate response in a patient taking corticosteroids is defined as a patient experiencing persistently active signs and symptoms of disease despite a history of at least one induction regimen including ≥ 40 mg / day equivalent of prednisone orally for 3-4 weeks or intravenously for 1 week.

59. 56. The method of claim 55, wherein the patient is unable to taper the corticosteroid to less than 10 mg prednisone equivalent orally daily without recurrence of active disease.

60. 56. The method of claim 55, wherein the patient's intolerance to corticosteroids results in Cushing's syndrome, osteopenia, osteoporosis, hyperglycemia, insomnia, or infection.

61. 56. The method of claim 55, wherein the patient experiencing an inadequate response to immunosuppressants experiences signs and symptoms of persistently active disease despite a history of a 90-day regimen of at least one of oral azathioprine, 6-mercaptopurine, injectable methotrexate, or tacrolimus.

62. 56. The method of claim 55, wherein the patient experiencing an inadequate response to the immunosuppressant experiences nausea, vomiting, abdominal pain, pancreatitis, liver enzyme abnormalities, lymphopenia, or infection.

63. Patients experiencing an inadequate response to biologic therapy a. At least one 6-week induction regimen of infliximab containing an intravenous dose of ≥ 5 mg / kg at weeks 0, 2, and 6; b. At least one 4-week induction regimen of adalimumab comprising one subcutaneous dose of 160 mg followed by one subcutaneous dose of 80 mg, or one subcutaneous dose of 80 mg followed by one subcutaneous dose of 40 mg, separated by at least 2 weeks; c. At least one 2-week induction regimen of golimumab comprising one subcutaneous dose of 200 mg followed by one subcutaneous dose of 100 mg, at least 2 weeks apart; d. At least one 6-week induction regimen of vedolizumab including an intravenous dose of 300 mg at weeks 0, 2, and 6 56. The method of claim 55, wherein the patient experiences signs and symptoms of persistently active disease despite a history of

64. 56. The method of claim 55, wherein the patient experiencing an inadequate response to biologic therapy experiences a recurrence of symptoms during maintenance dosing planned according to previous clinical benefit.

65. 56. The method of claim 55, wherein the patient experiencing intolerance to biologic therapy experiences congestive heart failure due to infusion reaction, demyelination, or infection.

66. 1. A method of inducing and maintaining clinical remission of ulcerative colitis in a patient, comprising: a. administering orally to a patient once daily for at least 4 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. the patient achieves clinical remission within 4 weeks after administration of the first induction dose; c. After the final induction dose has been administered, administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof orally once daily, comprising 30 mg of upadacitinib or a 30 mg free base equivalent of a pharmaceutically acceptable salt thereof; d. administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; e. The method wherein the patient maintains clinical remission 52 weeks after administration of the first induction dose.

67. 1. A method of inducing and maintaining clinical remission of ulcerative colitis in a patient, comprising: a. administering orally to a patient once daily for at least 6 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. the patient achieves clinical remission within 6 weeks after administration of the first 45 mg induction dose; c. After the final induction dose has been administered, administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof orally once daily, comprising 30 mg of upadacitinib or a 30 mg free base equivalent of a pharmaceutically acceptable salt thereof; d. administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; e. The method wherein the patient maintains clinical remission 52 weeks after administration of the first induction dose.

68. 1. A method of inducing and maintaining clinical remission of ulcerative colitis in a patient, comprising: a. administering orally to a patient once daily for at least 8 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. the patient achieves clinical remission within 8 weeks after administration of the first 45 mg induction dose; c. After the final induction dose has been administered, administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof orally once daily, comprising 30 mg of upadacitinib or a 30 mg free base equivalent of a pharmaceutically acceptable salt thereof; d. administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; e. The method wherein the patient maintains clinical remission 52 weeks after administration of the first induction dose.

69. 1. A method for inducing and maintaining endoscopic improvement of ulcerative colitis in a patient, comprising: a. administering orally to a patient once daily for at least 8 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. the patient achieves endoscopic improvement within 8 weeks after administration of the first induction dose; c. After the final induction dose has been administered, administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof orally once daily, comprising 30 mg of upadacitinib or a 30 mg free base equivalent of a pharmaceutically acceptable salt thereof; d. administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; e. The method wherein the patient maintains clinical remission 52 weeks after administration of the first induction dose.

70. 1. A method of inducing and maintaining endoscopic remission of ulcerative colitis in a patient, comprising: a. administering orally to a patient once daily for at least 8 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. the patient achieves endoscopic remission within 8 weeks after administration of the first 45 mg induction dose; c. After the final induction dose has been administered, administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof orally once daily, comprising 30 mg of upadacitinib or a 30 mg free base equivalent of a pharmaceutically acceptable salt thereof; d. administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; e. The method wherein the patient maintains clinical remission 52 weeks after administration of the first induction dose.

71. 71. The method of any of claims 66 to 70, wherein the patient has moderate to severe active ulcerative colitis.

72. 71. The method of any of claims 66-70, wherein the patient is taking a corticosteroid at the time of the first induction dose.

73. 73. The method of claim 72, wherein corticosteroids are not used in clinical remission, endoscopic improvement, or endoscopic remission.

74. 71. The method of any of claims 66 to 70, wherein the patient has shown an inadequate response, loss of response or intolerance to one or more corticosteroids, immunosuppressants or biological treatments.

75. 75. The method of claim 74, wherein the immunosuppressant is selected from oral azathioprine, 6-mercaptopurine, injectable methotrexate, and tacrolimus.

76. 75. The method of claim 74, wherein the biological therapy is selected from infliximab, adalimumab, golimumab, and vedolizumab.

77. 75. The method of claim 74, wherein an inadequate response in a patient taking corticosteroids is defined as a patient experiencing persistently active signs and symptoms of disease despite a history of at least one induction regimen including ≥ 40 mg / day equivalent of prednisone orally for 3-4 weeks or intravenously for 1 week.

78. 75. The method of claim 74, wherein the patient is unable to taper the corticosteroid to less than 10 mg prednisone equivalent orally daily without recurrence of active disease.

79. 75. The method of claim 74, wherein the patient's intolerance to corticosteroids results in Cushing's syndrome, osteopenia, osteoporosis, hyperglycemia, insomnia, or infection.

80. 75. The method of claim 74, wherein the patient experiencing an inadequate response to immunosuppressants experiences signs and symptoms of persistently active disease despite a history of a 90-day regimen of at least one of oral azathioprine, 6-mercaptopurine, injectable methotrexate, or tacrolimus.

81. 75. The method of claim 74, wherein the patient experiencing intolerance to the immunosuppressant experiences nausea, vomiting, abdominal pain, pancreatitis, liver enzyme abnormalities, lymphopenia, or infection.

82. Patients experiencing an inadequate response to biologic therapy a. At least one 6-week induction regimen of infliximab containing an intravenous dose of ≥ 5 mg / kg at weeks 0, 2, and 6; b. At least one 4-week induction regimen of adalimumab comprising one subcutaneous dose of 160 mg followed by one subcutaneous dose of 80 mg, or one subcutaneous dose of 80 mg followed by one subcutaneous dose of 40 mg, separated by at least 2 weeks; c. At least one 2-week induction regimen of golimumab comprising one subcutaneous dose of 200 mg followed by one subcutaneous dose of 100 mg at least 2 weeks apart; or d. At least one 6-week induction regimen of vedolizumab including an intravenous dose of 300 mg at weeks 0, 2, and 6 75. The method of claim 74, wherein the patient experiences signs and symptoms of persistently active disease despite a history of

83. 75. The method of claim 74, wherein the patient experiencing an inadequate response to biologic therapy experiences a recurrence of symptoms during maintenance dosing planned according to previous clinical benefit.

84. 75. The method of claim 74, wherein the patient experiencing intolerance to biological therapy experiences congestive heart failure due to infusion reaction, demyelination, or infection.

85. 1. A method of inducing and maintaining clinical remission of ulcerative colitis in a patient, comprising: a. administering orally to a patient once daily for at least 4 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. the patient achieves clinical remission within 4 weeks after administration of the first induction dose; c. administering to the patient after the final induction dose a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 15 mg of upadacitinib or a 15 mg free base equivalent of a pharmaceutically acceptable salt thereof; d. administering at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof orally to the patient once daily; e. The method wherein the patient maintains clinical remission 52 weeks after administration of the first induction dose.

86. 1. A method of inducing and maintaining clinical remission of ulcerative colitis in a patient, comprising: a. administering orally to a patient once daily for at least 6 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. the patient achieves clinical remission within 6 weeks after administration of the first 45 mg induction dose; c. After the final induction dose has been administered, administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof orally once daily, comprising 15 mg of upadacitinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 15 mg of the free base; d. administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; e. The method wherein the patient maintains clinical remission 52 weeks after administration of the first induction dose.

87. 1. A method of inducing and maintaining clinical remission of ulcerative colitis in a patient, comprising: a. administering orally to a patient once daily for at least 8 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. the patient achieves clinical remission within 8 weeks after administration of the first 45 mg induction dose; c. After the final induction dose has been administered, administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof orally once daily, comprising 15 mg of upadacitinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 15 mg of the free base; d. administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; e. The method wherein the patient maintains clinical remission 52 weeks after administration of the first induction dose.

88. 1. A method for inducing and maintaining endoscopic improvement of ulcerative colitis in a patient, comprising: a. administering orally to a patient once daily for at least 12 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. the patient achieves endoscopic improvement within 12 weeks after administration of the first induction dose; c. After the final induction dose has been administered, administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof orally once daily, comprising 15 mg of upadacitinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 15 mg of the free base; d. administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; e. The method wherein the patient maintains clinical remission 52 weeks after administration of the first induction dose.

89. 1. A method of inducing and maintaining endoscopic remission of ulcerative colitis in a patient, comprising: a. administering orally to a patient once daily for at least 12 weeks an induction dose of upadacitinib or a pharmaceutically acceptable salt thereof comprising 45 mg of upadacitinib, or a pharmaceutically acceptable salt thereof, in an amount equivalent to 45 mg of the free base; b. the patient achieves endoscopic remission within 12 weeks after administration of the first 45 mg induction dose; c. After the final induction dose has been administered, administering to the patient a first maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof orally once daily, comprising 15 mg of upadacitinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 15 mg of the free base; d. administering to the patient at least one additional maintenance dose of upadacitinib or a pharmaceutically acceptable salt thereof; e. The method wherein the patient maintains clinical remission 52 weeks after administration of the first induction dose.

90. 90. The method of any of claims 85 to 89, wherein the patient has moderate to severe active ulcerative colitis.

91. 90. The method of any of claims 85-89, wherein the patient is taking a corticosteroid at the time of the first induction dose.

92. 92. The method of claim 91, wherein corticosteroids are not used in clinical remission, endoscopic improvement, or endoscopic remission.

93. 90. The method of any of claims 85 to 89, wherein the patient has shown an inadequate response, loss of response or intolerance to one or more corticosteroids, immunosuppressants or biological treatments.

94. 94. The method of claim 93, wherein the immunosuppressant is selected from oral azathioprine, 6-mercaptopurine, injectable methotrexate, and tacrolimus.

95. 94. The method of claim 93, wherein the biological therapy is selected from infliximab, adalimumab, golimumab, and vedolizumab.

96. 94. The method of claim 93, wherein an inadequate response in a patient taking corticosteroids is defined as a patient experiencing persistently active signs and symptoms of disease despite a history of at least one induction regimen including ≥ 40 mg / day equivalent of prednisone orally for 3-4 weeks or intravenously for 1 week.

97. 94. The method of claim 93, wherein the patient is unable to taper the corticosteroid to less than 10 mg prednisone equivalent orally daily without recurrence of active disease.

98. 94. The method of claim 93, wherein the patient's intolerance to corticosteroids results in Cushing's syndrome, osteopenia, osteoporosis, hyperglycemia, insomnia, or infection.

99. 94. The method of claim 93, wherein the patient experiencing an inadequate response to immunosuppressants experienced signs and symptoms of persistently active disease despite a history of a 90-day regimen of at least one of oral azathioprine, 6-mercaptopurine, injectable methotrexate, or tacrolimus.

100. 94. The method of claim 93, wherein the patient experiencing intolerance to the immunosuppressant experiences nausea, vomiting, abdominal pain, pancreatitis, liver enzyme abnormalities, lymphopenia, or infection.

101. Patients experiencing an inadequate response to biologic therapy a. At least one 6-week induction regimen of infliximab containing an intravenous dose of ≥ 5 mg / kg at weeks 0, 2, and 6; b. At least one 4-week induction regimen of adalimumab comprising one subcutaneous dose of 160 mg followed by one subcutaneous dose of 80 mg, or one subcutaneous dose of 80 mg followed by one subcutaneous dose of 40 mg, separated by at least 2 weeks; c. At least one 2-week induction regimen of golimumab comprising one subcutaneous dose of 200 mg followed by one subcutaneous dose of 100 mg, at least 2 weeks apart; d. At least one 6-week induction regimen of vedolizumab including an intravenous dose of 300 mg at weeks 0, 2, and 6 94. The method of claim 93, wherein the patient experiences signs and symptoms of persistently active disease despite a history of

102. 94. The method of claim 93, wherein the patient experiencing an inadequate response to biological therapy experiences a recurrence of symptoms during maintenance dosing planned according to previous clinical benefit.

103. 94. The method of claim 93, wherein the patient experiencing intolerance to biological therapy experiences congestive heart failure due to infusion reaction, demyelination, or infection.

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