Methods of Treating Subjects Suffering from Psoriatic Arthritis

Abstract

The present disclosure relates to the anti-IL-23p19 antibody hum13B8-b or an antigen-binding fragment thereof, and its use in the treatment of psoriatic arthritis.

Description

[Technical field]

[0001] The present disclosure relates to anti-IL-23p19 antibody hum13B8-b or its antigen-binding fragment, and its use in treating psoriatic arthritis.In some embodiments, the present disclosure relates to a method for treating psoriatic arthritis, wherein the treatment results in an improvement from baseline in both tender and swollen joint counts.In some embodiments, the present disclosure relates to a method for determining the effectiveness of anti-IL-23p19 antibody for treating psoriatic arthritis. [Background technology]

[0002] Psoriasis (PsO) is a chronic inflammatory skin disorder that affects approximately 1%-2% of the world's population. Psoriatic arthritis (PsA) is defined as a specific inflammatory arthritis associated with PsO. The exact prevalence is unknown, but estimates vary from 0.3%-1% of the population, with the observed prevalence of inflammatory arthritis varying from 6%-42% among PsO patients. Clinical features typically present as oligoarticular and mild disease. However, over time, PsA becomes polyarticular and is a severe disease in at least 20% of patients. Gladman et al., Ann. Rheum. Dis. 64(Suppl II): ii14-ii17 (2005). Symptoms include tenderness, pain, and stiffness in and around the joints, dactylitis, spondylitis, heel pain and swelling, nail deformities (discolored, split, or pitted), and generalized fatigue. PsA patients with polyarticular disease are at risk for disease progression. In addition to progression of clinical and radiological damage, PsA patients also experience a decline in health-related quality of life. Gladman et al. (2005).

[0003] Current treatment options for PsA include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, topical treatments (for the skin), phototherapy (for the skin), physical therapy, and disease-modifying antirheumatic drugs (DMARDs). There are two biologics approved for use in the treatment of PsA, and more recently, agents targeting interleukin-12 (IL-12) and IL-23. Methotrexate (MTX) is approved by the U.S. Food and Drug Administration (FDA) for the cutaneous condition PsO, but is frequently used off-label for PsA. Methotrexate has been reported to provide symptomatic relief in some patients with PsO involving multiple joints, but there is little scientific evidence to support its use as a disease-modifying agent for PsA. Summary of the Invention

[0004] Provided herein is a method of treating psoriatic arthritis comprising administering anti-IL-23p19 antibody hum13B8-b to a patient in need thereof, wherein the patient is administered an initial dose of the antibody subcutaneously at week 0, followed by subsequent doses every 12 weeks thereafter, and wherein the antibody hum13B8-b comprises (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2.

[0005] Also provided herein is a method of treating psoriatic arthritis comprising administering a therapeutically effective amount of the anti-IL-23p19 antibody hum13B8-b to a patient in need thereof, wherein the treatment results in at least a 20% improvement from baseline in tender and swollen joint counts, and wherein the antibody hum13B8-b comprises (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2.

[0006] Further provided herein is a method of treating psoriatic arthritis comprising administering a therapeutically effective amount of the anti-IL-23p19 antibody hum13B8-b to a patient in need thereof, wherein the treatment results in at least a 50% improvement from baseline in tender and swollen joint counts, and wherein the antibody hum13B8-b comprises (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2.

[0007] Further provided herein is a method of treating psoriatic arthritis comprising administering a therapeutically effective amount of the anti-IL-23p19 antibody hum13B8-b to a patient in need thereof, wherein the treatment results in at least a 70% improvement from baseline in tender and swollen joint counts, and wherein the antibody hum13B8-b comprises (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2.

[0008] Further provided herein is a method of determining efficacy of an anti-IL-23p19 antibody for treating psoriatic arthritis, comprising administering to a patient an initial dose of the antibody subcutaneously at week 0, followed by subsequent doses every 12 weeks thereafter, wherein the antibody hum13B8-b comprises (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1 and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2, and wherein an ACR20 response value of at least about 40% at week 24 or week 52 indicates efficacy of the antibody.

[0009] Further provided herein is a method of determining efficacy of an anti-IL-23p19 antibody for treating psoriatic arthritis, comprising administering to a patient an initial dose of the antibody subcutaneously at week 0, and subsequent doses every 12 weeks following the initial dose, wherein the antibody hum13B8-b comprises (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1 and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2, and wherein an ACR50 response value of at least about 20% at week 24 or week 52 indicates efficacy of the antibody.

[0010] Further provided herein is a method of determining efficacy of an anti-IL-23p19 antibody for treating psoriatic arthritis, comprising administering to a patient an initial dose of the antibody subcutaneously at week 0, and subsequent doses every 12 weeks following the initial dose, wherein the antibody hum13B8-b comprises (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1 and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2, and wherein an ACR70 response value of at least about 10% at week 24 or week 52 indicates efficacy of the antibody.

[0011] In some embodiments, provided herein is a method of determining efficacy of an anti-IL-23p19 antibody for treating psoriatic arthritis, comprising administering to a patient an initial dose of the antibody subcutaneously at week 0, followed by subsequent doses every 12 weeks thereafter, the antibody hum13B8-b comprising (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1 and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2, and wherein at least a 75% improvement in psoriasis area and severity index from baseline at week 52 is indicative of efficacy of the antibody. In some embodiments, at least a 90% improvement in psoriasis area and severity index from baseline at week 52 is indicative of efficacy of the antibody. In some embodiments, at least a 100% improvement in psoriasis area and severity index from baseline at week 52 is indicative of efficacy of the antibody.

[0012] In some embodiments, provided herein is a method of determining efficacy of an anti-IL-23p19 antibody for treating psoriatic arthritis, comprising administering to a patient an initial dose of the antibody subcutaneously at week 0, followed by subsequent doses every 12 weeks thereafter, and the antibody hum13B8-b comprises (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1 and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2, and wherein a reduction in DAS28-CRP score from baseline at week 52 indicates efficacy of the antibody. In some embodiments, the patient may experience a reduction in DAS28 score of 1, 2, 3, 4, 5, 6, 7, 8, or 9 units.

[0013] In some embodiments, provided herein is a method of determining efficacy of an anti-IL-23p19 antibody for treating psoriatic arthritis, comprising administering to a patient an initial dose of the antibody subcutaneously at week 0, followed by subsequent doses every 12 weeks thereafter, and wherein the antibody hum13B8-b comprises (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1 and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2, and wherein a statistically significant improvement in disease activity as determined by minimal disease activity (MDA) criteria at week 52 indicates efficacy of the antibody. [Brief description of the drawings]

[0014] [Figure 1] Figure 1 is a schematic diagram showing the study design. Abbreviations: B / l = baseline; LTE = long-term extension; mg = milligrams; PtGA = Patient Global Assessment; q = weekly; Tildra = tildrakizumab; Wk = weekly. [Diagram 2] Figure 2 shows the ACR20 / 50 / 70 of patients throughout the treatment period and at each time point up to week 52. Abbreviations: Q4W: every 4 weeks, Q12W: every 12 weeks, TIL: tildrakizumab. [Diagram 3]Figure 3 shows the ACR20 / 50 / 70 of patients throughout the treatment period and at each time point through week 24. Abbreviations: PBO: placebo, Q4W: every 4 weeks, Q12W: every 12 weeks, TIL: tildrakizumab. *P < 0.05; †P < 0.001; P < 0.0001 vs. placebo. [Figure 4] Figure 4 shows the response rate of minimal disease activity across the entire treatment period and at each time point from baseline to week 52 in patients with PsA. Error bars represent 95% confidence intervals. Abbreviations: PsA: psoriatic arthritis, Q4W: every 4 weeks, Q12W: every 12 weeks, TIL: tildrakizumab. [Diagram 5] Figure 5 shows the PASI 75 / 90 / 100 response rates throughout the treatment period and at each time point through week 52. Patient response rates were calculated as baseline BSA ≥ 3%. Black symbols corresponding to p-values ​​were analyzed using missing value imputation methods for missing responses. P-values ​​are based on the Cochran-Mantel-Haenszel test for missing value imputation datasets (past anti-TNF use and baseline weights as stratification factors). *P < 0.05; †P < 0.001; P < 0.0001 vs placebo. Abbreviations: BSA: body surface area; PASI: Psoriasis Area and Severity Index; Q4W: every 4 weeks; Q12W: every 12 weeks; TIL: tildrakizumab. [Figure 6] Figure 6 shows the DAS28-CRP response rate over the entire treatment period and at each time point. Error bars represent 95% confidence intervals. Abbreviations: Q4W: every 4 weeks, Q12W: every 12 weeks, TIL: tildrakizumab. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] The present disclosure relates to an anti-IL-23p19 antibody hum13B8-b or an antigen-binding fragment thereof, and its use in treating psoriatic arthritis. In some embodiments, a method of treating psoriatic arthritis is provided herein, comprising administering an anti-IL-23p19 antibody hum13B8-b to a patient in need thereof, wherein the patient is administered a first dose of the antibody subcutaneously at week 0, followed by subsequent doses every 12 weeks thereafter, and the antibody hum13B8-b comprises (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2.

[0016] As utilized in accordance with this disclosure, unless otherwise indicated, all technical and scientific terms shall be understood to have the same meaning as commonly understood by those of ordinary skill in the art. Unless otherwise required by context, singular terms shall include the plural and plural terms shall include the singular.

[0017] The term "antibody" as used herein refers to a protein capable of recognizing and specifically binding to an antigen. A normal or conventional mammalian antibody comprises a tetramer, which typically consists of two identical pairs of polypeptide chains, each pair consisting of one "light chain" (typically having a molecular weight of about 25 kDa) and one "heavy chain" (typically having a molecular weight of about 50-70 kDa). The terms "heavy chain" and "light chain" as used herein refer to any immunoglobulin polypeptide having sufficient variable domain sequence to confer specificity for a target antigen. The amino-terminal portion of each light and heavy chain typically contains a variable domain of about 100-110 or more amino acids responsible for antigen recognition. The carboxyl-terminal portion of each chain typically defines a constant domain responsible for effector function. Thus, in naturally occurring antibodies, the full-length heavy chain immunoglobulin polypeptide comprises a variable domain (V H ) and three constant domains (C H1 , C H2 , and C H3 ), and C H1 and C. H2 and a hinge region between VH The domain is located at the amino terminus of the polypeptide and is C H3 The domain is at the carboxyl terminus, and a full-length light chain immunoglobulin polypeptide comprises a variable domain (VL) and a constant domain (CL), where V L The domain is located at the amino terminus of the polypeptide and is C L The domain is at the carboxyl terminus.

[0018] Within full-length light and heavy chains, the variable and constant domains are typically joined by a "J" region of about 12 or more amino acids, with the heavy chain also including a "D" region of about 10 more amino acids. The variable regions of each light / heavy chain pair typically form the antigen-binding site. The variable domains of naturally occurring antibodies typically exhibit the same general structure of relatively conserved framework regions (FR) joined by three hypervariable regions, also called complementarity determining regions or CDRs. The CDRs in the two chains of each pair are typically aligned by the framework regions, which may enable binding to a specific epitope. From the amino terminus to the carboxyl terminus, both the light and heavy chain variable domains typically include the domains FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4.

[0019] The term "antigen-binding fragment" as used herein refers to a portion of an intact antibody and / or to the antigen-determining variable domain of an intact antibody. It is known that the antigen-binding function of an antibody can be performed by a fragment of a full-length antibody. Examples of antibody fragments include, but are not limited to, Fab, Fab', F(ab')2, and Fv fragments formed from antibody fragments, linear antibodies, single-chain antibodies, diabodies, and multispecific antibodies.

[0020] In a specific embodiment, the anti-IL-23p19 antibody hum13B8-b is tildrakizumab. As used herein, the term "tildrakizumab" refers to a humanized anti-IL-23p19 monoclonal antibody, also known as SCH 900222 or MK-3222. Tildrakizumab is a high affinity (297 picomolar [pM]) humanized immunoglobulin G1 / kappa (IgG1 / n) antibody that specifically binds to the p19 protein of the IL-23 heterodimer, but not to human IL-12 (IL-12 / 23p40 and IL12p35 heterodimer) or human IL-12 / 23p40.

[0021] In certain embodiments, tildrakizumab comprises a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1, and a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2, as disclosed in U.S. Patent Nos. 8,404,813 and 8,293,883, the disclosures of each of which are incorporated herein by reference in their entireties. In other embodiments, tildrakizumab or an antigen-binding fragment thereof comprises a heavy chain variable domain and a light chain variable domain, wherein the heavy chain variable domain comprises CDR1, CDR2, and CDR3 of the amino acid sequences of SEQ ID NOs:3-5, and the light chain variable domain comprises CDR1, CDR2, CDR3 of the amino acid sequences of SEQ ID NOs:6-8.

[0022] As used herein, the terms "subject" and "patient" are interchangeable. In some embodiments, a subject and / or patient is a mammal.

[0023] A "disorder" is any condition that would benefit from treatment with an antibody of the present disclosure. "Disorder" and "condition" are used interchangeably herein and include chronic and acute disorders or diseases, including pathological conditions that predispose a patient to the disorder in question.

[0024] As used herein, the term "treatment" or "treating" refers to both therapeutic treatment as well as prophylactic or preventative measures. Patients in need of treatment include those with psoriatic arthritis, as well as those susceptible to psoriatic arthritis or those in whom psoriatic arthritis is to be prevented.

[0025] As used herein, the term "administration" or "administering" refers to providing, contacting, and / or delivering an antibody or fragment thereof by any suitable route to achieve a desired effect. Administration may include, but is not limited to, oral administration, sublingual administration, parenteral administration (e.g., intravenous, subcutaneous, intradermal, intramuscular, intra-articular, intra-arterial, intrasynovial, intrasternal, intrathecal, intralesional, or intracranial injection), transdermal administration, topical administration, buccal administration, rectal administration, vaginal administration, intranasal administration, ophthalmic administration, inhalation, and implantation.

[0026] In some embodiments, the anti-IL-23p19 antibody hum13B8-b, or an antigen-binding fragment thereof, is administered every 2 weeks, every 4 weeks, every 6 weeks, every 8 weeks, every 10 weeks, or every 12 weeks.

[0027] As used herein, the term "week 0" refers to the first day that the anti-IL-23p19 antibody hum13B8-b, or an antigen-binding fragment thereof, is administered.

[0028] In some embodiments, the anti-IL-23p19 antibody hum13B8-b, or an antigen-binding fragment thereof, is administered over a 2 week treatment period, a 4 week treatment period, a 6 week treatment period, a 8 week treatment period, a 12 week treatment period, a 24 week treatment period, a 36 week treatment period, a 48 week treatment period, a 60 week treatment period, a 72 week treatment period, or a treatment period of one year or more.

[0029] The therapeutic dose of the anti-IL-23p19 antibody hum13B8-b or antigen-binding fragment thereof will vary in part depending on the patient's body size (weight, body surface, or organ size) and condition (age and general health). In some embodiments, the patient is administered one or more doses of the anti-IL-23p19 antibody hum13B8-b or antigen-binding fragment thereof, where the dose is 20 mg, 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, 160 mg, 180 mg, or 200 mg. In some embodiments, the initial dose and subsequent doses of the anti-IL-23p19 antibody hum13B8-b or antigen-binding fragment thereof are the same. In some embodiments, the initial dose and subsequent doses of the anti-IL-23p19 antibody hum13B8-b or antigen-binding fragment thereof are different. In some embodiments, the initial dose is 100 mg. In some embodiments, the initial dose is 200 mg. In some embodiments, the subsequent dose is 100 mg. In some embodiments, the subsequent dose is 200 mg. In some embodiments, the first dose and subsequent doses are 100 mg. In some embodiments, the first dose and subsequent doses are 200 mg.

[0030] In some embodiments, provided herein is a method of treating psoriatic arthritis comprising administering a therapeutically effective amount of the anti-IL-23p19 antibody hum13B8-b to a patient in need thereof, wherein the treatment results in at least a 20%, at least a 50%, or at least a 70% improvement from baseline in tender joint counts and swollen joint counts, and wherein the antibody hum13B8-b comprises (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1 and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2.

[0031] For joint counts, five clinical patterns have been described in patients with PsA: distal interphalangeal joint (DIP), asymmetric oligoarticular, symmetric polyarticular, spondylitis, and destructive arthritis. Peripheral joints are assessed for tenderness and swelling. There are no validated scales to assess peripheral joints in PsA, and the scale used is the ACR joint count, originally developed for the evaluation of patients with rheumatoid arthritis (RA). ACR joint counts range from 28, 44, 68, and 78 for tenderness and 28, 44, 66, and 76 for swelling (swelling cannot be felt in the hip joint, and the hip joint is excluded from the evaluation of swelling). The ACR joint count, consisting of a 68 tender joint count and a 66 swollen joint count, includes the majority of joints affected by PsA and can be easily performed at the clinic visit. This includes the temporomandibular joint, sternoclavicular joint, acromioclavicular joint, shoulder joint, elbow joint, wrist (including the carpometacarpal and intercarpal joints as one unit), metacarpophalangeal joint (MCP), proximal interphalangeal joint (PIP), DIP, hip joint, knee joint, talocrural joint, transverse tarsal joint (including the subtalar joint), metatarsophalangeal joint, and interphalangeal joints of the toes (the proximal and distal joints of each toe count as one unit).

[0032] The American College of Rheumatology 20 / 50 / 70 response criteria (ACR20 / 50 / 70) assess the proportion of subjects showing at least 20%, 50%, or 70% improvement from baseline in tender joints (68) and swollen joints (66) and associated improvement in three of five other measures: 1) PGA of disease activity (measured using a VAS), 2) PtGA of disease activity (measured using a VAS), 3) Patient Pain Assessment (measured using a VAS), 4) Patient Self-Rated Disability (measured using the HAQ-DI), and 5) Acute Phase C-Reactive Protein (CRP).

[0033] C-reactive protein (CRP) or high-sensitivity C-reactive protein (hsCRP) is an acute phase reactant, a protein produced by the liver and released into the blood within hours after the onset of tissue injury, infection, or other causes of inflammation, such as autoimmune disease. Significantly increased levels are observed in patients with active psoriatic arthritis and serve as one of the biomarkers of psoriatic arthritis pathology.

[0034] Physician Global Assessment of Disease Activity (PGA) refers to an assessment in which a physician assesses the subject's PsA status using a visual analog scale (VAS). Subjects are assessed according to their current arthritis status. The VAS is set with verbal descriptors ranging from "very good" to "very bad."

[0035] Patient Global Assessment of Disease Activity (PtGA) refers to subjects' assessment of their current overall state of PsA ("Taking into account all the effects that arthritis has on you, on average, how are you feeling today?") using a VAS with verbal descriptors ranging from "very good" to "very bad."

[0036] Patient pain assessment involves subjects rating their current pain level using a VAS ("How bad is the pain caused by your arthritis right now?"). Subjects rate their current pain on a scale set up with verbal descriptors ranging from "no pain" to "worst pain."

[0037] Patient self-rated disability refers to subjects' assessment of their own global disability over the past week using the HAQ-DI questionnaire.

[0038] In some embodiments, the methods disclosed herein result in at least a 20%, at least a 50%, or at least a 70% improvement from baseline in at least three of five parameters selected from the group consisting of: (i) physician global assessment of disease activity, (ii) patient global assessment of disease activity, (iii) patient pain assessment, (iv) patient self-rated disability, and (v) acute phase CRP.

[0039] The Health Assessment Questionnaire-Disability Index (HAQ-DI) is designed to assess a patient's usual abilities using standard equipment. For patients, the HAQ-DI is usually self-explanatory and requires little explanation. The eight categories assessed by the HAQ-DI are 1) dressing and grooming, 2) sitting up, 3) eating, 4) walking, 5) hygiene, 6) reaching, 7) grip strength, and 8) general daily activities. For each of these categories, patients report how much difficulty they have in performing two or three specific activities. The time frame for the disability questions is the past week, and each question can be scored as 0 (no difficulty), 1 (some difficulty), 2 (a lot of difficulty), or 3 (unable to perform the activity). The use of assistive devices and equipment for these activities is also recorded. Use of equipment or assistive devices results in a minimum score of 2 for that category. The disability index score is the average of the eight category scores. If three or more (25%) of the categories are missing, the scale is not scored. If no category has fewer than two, divide the sum of the categories by the number of categories answered. The higher the score, the greater the disability.

[0040] The Disease Activity Score 28-item C-reactive protein (DAS28-CRP) refers to a measure of disease activity assessed on 28 joints including shoulder, elbow, wrist, MCP (1-5), PIP (1-5), and knee, with all 14 joints assessed on each side of the body. It is a composite score derived from examination of the 28 joints for swelling and tenderness, a global assessment of pain and overall condition using a VAS, and a blood marker of inflammation (hsCRP).

[0041] The Leeds dactylometer refers to a validated tool for assessing dactylitis. The dactylometer is used to measure the circumference of the base of the affected finger and compare it to the contralateral finger. The LDI is a measure of this comparison, with a tenderness score (0=not tender, 1=tender, 2=painfully tender, and 3=unbearably tender) for the joint considered to be affected by dactylitis (dactylitis is defined as a 10% difference in circumference ratio of the affected finger compared to the contralateral finger). The LEI examines tenderness at six sites: the lateral epicondyle of the humerus, the medial condyle of the femur, and two sites each (left and right) at the Achilles tendon insertion. For each site of enthesitis, an assessment of the adjacent joint is made for tenderness and soft tissue swelling, scored 1 if present. The LEI score range is 0-6.

[0042] The Psoriasis Area and Severity Index (PASI) is a measure of the average redness, thickness, and scalyness of lesions (each rated on a scale of 0 to 4), weighted by the area of ​​involvement. A 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) is the current benchmark primary endpoint for most clinical trials in psoriasis.

[0043] Minimal Disease Activity (MDA) is a measure of disease remission. Patients are classified as having achieved MDA if they meet five of seven criteria: tender joint count ≦1, swollen joint count ≦1, Psoriasis Activity and Severity Index ≦1 or body surface area ≦3, patient pain visual analog scale (VAS) score ≦15, patient global disease activity VAS score ≦20, Health Assessment Questionnaire (HAQ) score ≦0.5, and tender enthesitis points ≦1.

[0044] As used herein, the term "pharmaceutical composition" or "therapeutic composition" refers to a compound or composition capable of inducing a desired therapeutic effect when properly administered to a patient. One embodiment of the present disclosure provides a pharmaceutical composition comprising a pharma- ceutical acceptable carrier and a therapeutically effective amount of at least one antibody of the present disclosure.

[0045] As used herein, the term "pharmaceutically acceptable carrier" or "physiologically acceptable carrier" refers to one or more formulation materials suitable for achieving or enhancing delivery of one or more antibodies of the present disclosure.

[0046] Provided herein are pharmaceutical compositions that contain tildrakizumab alone or in combination with a preventive agent, a therapeutic agent, and / or a pharmaceutically acceptable carrier. The pharmaceutical compositions provided herein that contain tildrakizumab are intended for, but are not limited to, the diagnosis, detection, or monitoring of a disorder, the prevention, treatment, management, or amelioration of a disorder or one or more symptoms thereof, and / or for use in research. The formulation of pharmaceutical compositions alone or in combination with a preventive agent, a therapeutic agent, and / or a pharmaceutically acceptable carrier is known to those skilled in the art.

[0047] In some embodiments, provided herein is a method of determining efficacy of an anti-IL-23p19 antibody for treating psoriatic arthritis, comprising administering to a patient an initial dose of the antibody subcutaneously at week 0, followed by subsequent doses every 12 weeks thereafter, the antibody hum13B8-b comprising (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1 and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2, and an ACR20 response value of at least about 40% at week 24 or week 52 is indicative of efficacy of the antibody. In some embodiments, an ACR20 response value of at least about 50% at week 24 or week 52 is indicative of efficacy of the antibody. In some embodiments, an ACR20 response value of at least about 60% at week 24 or week 52 is indicative of efficacy of the antibody.

[0048] In some embodiments, provided herein is a method of determining efficacy of an anti-IL-23p19 antibody for treating psoriatic arthritis, comprising administering to a patient an initial dose of the antibody subcutaneously at week 0, followed by subsequent doses every 12 weeks thereafter, the antibody hum13B8-b comprising (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1 and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2, and an ACR50 response value of at least about 20% at week 24 or week 52 is indicative of efficacy of the antibody. In some embodiments, an ACR50 response value of at least about 25% at week 24 or week 52 is indicative of efficacy of the antibody. In some embodiments, an ACR50 response value of at least about 30% at week 24 or week 52 is indicative of efficacy of the antibody.

[0049] In some embodiments, provided herein is a method of determining efficacy of an anti-IL-23p19 antibody for treating psoriatic arthritis, comprising administering to a patient an initial dose of the antibody subcutaneously at week 0, followed by subsequent doses every 12 weeks thereafter, the antibody hum13B8-b comprising (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1 and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2, and an ACR70 response value of at least about 10% at week 24 or week 52 is indicative of efficacy of the antibody. In some embodiments, an ACR70 response value of at least about 12% at week 24 is indicative of efficacy of the antibody. In some embodiments, an ACR70 response value of at least about 15% at week 24 or week 52 is indicative of efficacy of the antibody.

[0050] In some embodiments, provided herein is a method of determining efficacy of an anti-IL-23p19 antibody for treating psoriatic arthritis, comprising administering to a patient an initial dose of the antibody subcutaneously at week 0, followed by subsequent doses every 12 weeks thereafter, the antibody hum13B8-b comprising (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1 and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2, and wherein at least a 75% improvement in psoriasis area and severity index from baseline at week 52 is indicative of efficacy of the antibody. In some embodiments, at least a 90% improvement in psoriasis area and severity index from baseline at week 52 is indicative of efficacy of the antibody. In some embodiments, a 100% improvement in psoriasis area and severity index from baseline at week 52 is indicative of efficacy of the antibody.

[0051] In some embodiments, provided herein is a method of determining efficacy of an anti-IL-23p19 antibody for treating psoriatic arthritis, comprising administering to a patient an initial dose of the antibody subcutaneously at week 0, followed by subsequent doses every 12 weeks thereafter, and the antibody hum13B8-b comprises (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1 and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2, and wherein a reduction in DAS28-CRP score from baseline at week 52 indicates efficacy of the antibody. In some embodiments, the patient may experience a reduction in DAS28 score of 1, 2, 3, 4, 5, 6, 7, 8, or 9 units.

[0052] In some embodiments, provided herein is a method of determining efficacy of an anti-IL-23p19 antibody for treating psoriatic arthritis, comprising administering to a patient an initial dose of the antibody subcutaneously at week 0, followed by subsequent doses every 12 weeks thereafter, and wherein the antibody hum13B8-b comprises (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1 and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2, and wherein a statistically significant improvement in disease activity as determined by minimal disease activity (MDA) criteria at week 52 indicates efficacy of the antibody. EXAMPLES

[0053] The following examples are illustrative of certain embodiments of the present disclosure and various uses thereof. They are provided for illustrative purposes only and should not be construed as limiting the scope of the disclosure in any way. [Example 1]

[0054] Administration of Tildrakizumab in Subjects with Active Psoriatic Arthritis

[0055] 1. Study Design A randomized, double-blind, placebo-controlled, multiple-dose, phase 2b study was conducted to evaluate the efficacy of four dose groups of tildrakizumab administered by subcutaneous injection in subjects with active PsA (NCT02980692). Subjects with active PsA were randomized 1:1:1:1:1 to receive tildrakizumab 200 milligrams (mg) by subcutaneous (SC) injection every 4 weeks (q) through week 52; tildrakizumab 200 mg SC every 12 weeks through week 52; tildrakizumab 100 mg SC every 12 weeks through week 52; tildrakizumab 20 mg SC at weeks 0 and 12, followed by tildrakizumab 200 mg every 12 weeks through week 24 and thereafter through week 52; or placebo SC at weeks 0, 4, 8, 12, 16, 20, and 24, followed by tildrakizumab 200 mg every 12 weeks through week 52. All subjects received injections every 4 weeks; subjects randomized to the active treatment group every 12 weeks received placebo injections at weeks 4, 8, 16, 20, 28, 32, 40, and 44.

[0056] The study consisted of a screening period (days -28 to 0), part 1, a double-blind placebo-controlled period (weeks 1 to 24), part 2, a double-blind follow-up period (weeks 25 to 52), and part 3, a 20-week washout period (weeks 53 to 72). Subjects did not receive tildrakizumab during the washout period. Subjects who demonstrated a clinical response to treatment at week 24 (defined as ≥20% improvement from baseline in both swollen and tender joint counts and ≥20% improvement from baseline in Patient Global Assessment of Disease Activity [PtGA]) were enrolled in part 2 of the study. Subjects who received tildrakizumab (100 mg q12 weeks or 200 mg [q4 and q12 weeks] dose groups) during part 1 but did not demonstrate a clinical response to treatment at week 24 discontinued study drug. Subjects who received placebo or 20 mg tildrakizumab during part 1 and did not have a clinical response to treatment at week 24 entered part 2 and received 200 mg tildrakizumab every 12 weeks through week 52. Part 2 subjects discontinued study treatment because they did not achieve sufficient clinical benefit at any time point after week 24.

[0057] The primary endpoint was measured by the proportion of subjects achieving a 20% improvement from baseline in the American College of Rheumatology response criteria (ACR20) response rate at weeks 24 and 52. Secondary efficacy endpoints included ACR50, ACR70 response rates, and components of ACR response, proportion of subjects requiring adjustment of background therapy, proportion of subjects achieving DAS28-CRP < 3.2, proportion of subjects achieving minimal disease activity (MDA) criteria, change from baseline in Leeds Dactylitis Index (LDI) and Leeds Enthesitis Index (LEI), change from baseline in HAQ-DI, and 75% / 90% / 100% improvement in Psoriasis Area and Severity Index (PASI). PK and immunogenicity of tildrakizumab and treatment-emergent adverse events (TEAEs) were also evaluated.

[0058] 2. Selection of study population The study population included subjects aged 18 years or older who were diagnosed with PsA (according to Classification of Psoriatic Arthritis [CASPAR] criteria) at screening and baseline with symptoms of 3 or more tender joints and 3 or more swollen joints for at least 6 months.

[0059] Subjects were excluded from the study if their aspartate aminotransferase (AST) or alanine aminotransferase (ALT) was ≥2 times the upper limit of normal (ULN), their creatinine was ≥1.5 times the ULN, their serum direct bilirubin was ≥1.5 mg / dL, their white blood cell (WBC) count was <3.0 × 103 / μL, or their rheumatoid factor test results were positive.

[0060] Table 1 provides a summary of demographic characteristics by treatment for selected subjects. Table 2 provides a summary of baseline disease characteristics for selected subjects. N is the number of subjects in the treatment group analysis population and n is the number of subjects in a given category with no missing values. Baseline is defined as the last available value before the first dose of study drug. [Table 1] Summary of demographic characteristics by treatment full analysis set TIFF0007628962000001.tif228159

[0061] TIFF0007628962000002.tif232159[Table 2] Full analysis set of baseline disease characteristics TIFF0007628962000003.tif241158

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[0064] 3.Statistical analysis The primary efficacy analysis population was the Full Analysis Set (FAS), defined as all randomized subjects who received at least one dose of the investigational medicinal product (IMP). The primary analysis was based on the Cochran-Mantel-Haenszel test, incorporating past anti-TNF use and baseline weights as stratification factors, to compare the response rates for the primary endpoint (ACR20 at weeks 24 and 52) between placebo and each active dose group. In addition, the difference in response rates between placebo and each active dose group and the corresponding confidence intervals (CIs) were estimated. Early withdrawals and any other subjects with incomplete data at week 24 were classified as non-responders for the primary endpoint (ACR20). Subjects who showed only a minimal response to treatment at week 16 (defined as a <10% improvement from baseline in either swollen or tender joint counts) may have received background medication adjusted according to the maximum tolerated daily dose and continued in the study. Any subjects requiring these adjustments were counted as non-responders for the primary analysis.

[0065] The analysis of the primary outcome was based on the FAS. Sensitivity analyses were performed based on the PPAS. [Example 4]

[0066] Results up to 24 weeks

[0067] A summary of subject status at week 24 is shown in Table 3. The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. The full analysis set consisted of all randomized subjects who received at least one dose of investigational drug (IMP). The per protocol analysis set consisted of all subjects in the full analysis set without significant protocol deviations that could affect the validity of the data for the primary efficacy variable. Percentages were based on the number of randomized subjects excluding completers and discontinuers (percentages were based on the number of subjects in the safety analysis set). Part 1 was the double-blind, placebo-controlled period from baseline to week 24, and part 2 was the double-blind follow-up period from week 25 to week 52. [Table 3] Summary of subject status at 24 weeks TIFF0007628962000006.tif205158

[0068] Cochran-Mantel Haenszel (CMH) analysis of ACR20 response rates through week 24 is shown in Table 4. ACR20 was calculated as ≥20% improvement from baseline in tender and swollen joint counts and ≥20% improvement from baseline in three of the remaining five ACR core set scales: patient and physician global assessment, pain, disability, and acute CRP. Subjects who received tildrakizumab (100 mg q12 weeks or 200 mg [q4 and q12 weeks] dose groups) during part 1 but did not demonstrate a clinical response to treatment at week 24 discontinued study drug and entered a washout period as per protocol. Week 24 assessments for subjects who discontinued study drug were recorded at week 52 / EOT. Two-sided 95% CIs and p values ​​are based on CMH tests with stratification factors of anti-TNF use and baseline weights. If the Mantel-Fleiss criterion was <5, pairwise comparisons were based on Fisher's exact test after collapsing across levels of the stratification factor. This is noted with an "*" for the p-value. Baseline is defined as the last available value before the first dose of study drug. [Table 4] CMH analysis of ACR20 response rate up to 24 weeks (no response = non-response) - Full analysis set TIFF0007628962000007.tif227159

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[0073] Table 5 shows the CMH analysis of ACR50 response rates through week 24. ACR50 was calculated as ≥50% improvement from baseline in tender and swollen joint counts and ≥50% improvement from baseline in three of the remaining five ACR Core Set scales: patient and physician global assessment, pain, disability, and acute CRP. The ACR50 analysis was performed in the same manner as described above for the ACR20 analysis.

[0074] Subjects who receive tildrakizumab (100 mg q12 weeks or 200 mg [q4 and q12 weeks] dose groups) during part 1 but do not demonstrate a clinical response to treatment at week 24 will discontinue study drug and enter a washout period per protocol. Week 24 assessments for subjects who discontinue study drug will be recorded at week 52 / EOT. These assessments will be reported as part of the week 24 visit. Two-sided 95% CIs and p-values ​​are based on CMH tests with anti-TNF use and baseline weights as stratification factors. If the Mantel-Fleiss criterion is less than 5, pairwise comparisons will be based on Fisher exact tests after collapsing between levels of stratification factors. This will be noted with an “*” for p-values. Baseline is defined as the last available value before the first dose of study drug. [Table 5] CMH analysis of ACR50 response rate up to 24 weeks (no response = non-response) - Full analysis set TIFF0007628962000012.tif227158

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[0079] Table 6 shows the CMH analysis of ACR70 response rates through week 24. ACR70 was calculated as ≥70% improvement from baseline in tender and swollen joint counts and ≥70% improvement from baseline in three of the remaining five ACR Core Set scales: patient and physician global assessment, pain, disability, and acute CRP. The ACR70 analysis was performed in the same manner as described above for the ACR20 analysis. [Table 6] CMH analysis of ACR70 response rate up to 24 weeks (no response = non-response) - Full analysis set TIFF0007628962000017.tif223158

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[0084] 4. Results up to 52 weeks Of 500 patients screened, 391 were randomized and received at least one dose of drug. The proportion of ACR20 / 50 / 70 responders was superior with tildrakizumab compared with placebo through week 24. After week 24, responders further increased with tildrakizumab 20→200 mg Q12W and placebo→200 mg Q12W through week 52 (Figures 2 and 3). Additional efficacy results are shown in Table 7.

[0085] MDA was assessed throughout the study, and patients achieved an MDA response if 5 of 7 criteria were met. Baseline disease characteristics associated with MDA changed little between study arms (Table 8). By week 24, MDA status was achieved in significantly more patients receiving tildrakizumab compared with placebo (0% to 24%–39% vs. 0% to 7%, p<0.02 for all arms). This proportion further increased with continued tildrakizumab treatment through week 52 (45%–64%), including in patients who switched from placebo to tildrakizumab (47%) (Figure 4).

[0086] Treatment with tildrakizumab significantly increased the proportion of PASI 75 / 90 / 100 responders compared with placebo at week 24. This proportion continued to increase thereafter and remained stable through week 52 (Figure 5). Similarly, in patients who switched from placebo → tildrakizumab 200 mg Q12W or who were titrated up from tildrakizumab 20 → 200 mg Q12W after week 24, PASI 75 / 90 / 100 response rates increased through week 36 and remained stable through week 52. Improvement in PASI 75 skin responses with tildrakizumab 200 mg Q12W was significant compared with placebo as early as week 4. Tildrakizumab had a tolerable safety profile through week 52.

[0087] DAS28-CRP has been shown to be reliable in PsA, and patients who achieved a score <3.2 were considered responders. At baseline, disease characteristics were consistent across treatment groups, with 1.3%–7.7% of patients having a DAS28-CRP score <3.2 (Table 9). At week 24, DAS28-CRP response rates increased across all tildrakizumab treatment groups compared with placebo (Figure 6). After week 24, response rates continued to increase and were sustained through week 52, including in patients who switched from placebo to tildrakizumab.

[0088] Overall, 50.4% / 39.9% and 2.3% / 1.0% of patients experienced TEAEs and serious AEs from baseline to week 24 / week 25 to week 52, respectively. The most common TEAEs were nasopharyngitis (total tildrakizumab 5.4% / 4.2% vs. placebo 6.3% / 3.8%) and upper respiratory tract infection (total tildrakizumab 3.8% / 4.2% vs. placebo 1.3% / 0.0%). One patient (0.3%) discontinued before week 24 due to hypertension. One case of pyelonephritis and urinary tract infection was reported in the TIL 100 mg Q12W group and one case of chronic tonsillitis was reported in the TIL 20 mg Q12W group from baseline to week 24. One malignancy was reported in the TIL 20 mg → 200 mg Q12W group at week 25 → 52. There were no deaths or major adverse cardiac events. [Table 7] Clinical efficacy at week 52 (W52) TIFF0007628962000022.tif106170[Table 8] Baseline disease characteristics associated with minimal disease activity at week 52 TIFF0007628962000023.tif105170[Table 9] Baseline disease characteristics associated with DAS28-CRP TIFF0007628962000024.tif140170

[0089] 5. Conclusion: Tildrakizumab showed surprisingly high efficacy in this clinical trial with Q12Wk administration regimen. Tildrakizumab was found to be significantly more effective than placebo in treating joint symptoms of active psoriatic arthritis as measured by ACR20, ACR50, and ACR70 response criteria. Although the present disclosure has been described with reference to various embodiments, those skilled in the art will understand that variations and modifications occur. Accordingly, the appended claims are intended to cover all such equivalent variations that are within the scope of the present disclosure as claimed. Moreover, the section headings used herein are for organizational purposes only and should not be construed as limiting the subject matter described.

[0090] Each embodiment described herein may be combined with any other embodiment or embodiment unless expressly stated to the contrary. In particular, any feature or embodiment indicated as being preferred or advantageous may be combined with any other feature or embodiment indicated as being preferred or advantageous unless expressly stated to the contrary.

Claims

1. 1. A pharmaceutical composition for use in a method for treating psoriatic arthritis comprising the anti-IL-23p19 antibody hum13B8-b, The antibody hum13B8-b, (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1; (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2; wherein the method comprises administering to a patient in need thereof the antibody hum13B8-b; and wherein the patient receives a first dose of the antibody subcutaneously at week 0, followed by subsequent doses subcutaneously over a maximum of 72 hours every 12 weeks for at least 24 weeks; Pharmaceutical compositions.

2. The pharmaceutical composition of claim 1 , wherein the initial dose and the subsequent doses are the same.

3. The pharmaceutical composition of claim 1 , wherein the initial dose and the subsequent dose are different.

4. 2. The pharmaceutical composition of claim 1, wherein the initial dose is 100 mg.

5. 2. The pharmaceutical composition of claim 1, wherein the initial dose is 200 mg.

6. 2. The pharmaceutical composition of claim 1, wherein the subsequent dose is 100 mg.

7. 2. The pharmaceutical composition of claim 1, wherein the subsequent dose is 200 mg.

8. 3. The pharmaceutical composition of claim 2, wherein the initial dose and the subsequent doses are 100 mg.

9. 3. The pharmaceutical composition of claim 2, wherein the initial dose and the subsequent doses are 200 mg.

10. 4. The pharmaceutical composition of claim 3, wherein the initial dose is 100 mg and the subsequent dose is 200 mg.

11. 4. The pharmaceutical composition of claim 3, wherein the initial dose is 200 mg and the subsequent doses are 100 mg.

12. 2. The method of claim 1, wherein the subsequent doses are administered every 12 weeks for up to at least 36 weeks.

13. 2. The method of claim 1, wherein the subsequent doses are administered every 12 weeks for up to at least 48 weeks.

14. 2. The method of claim 1, wherein the subsequent doses are administered every 12 weeks for up to at least 60 weeks.

15. 2. The method of claim 1, wherein the subsequent doses are administered every 12 weeks for up to at least 72 weeks.

16. 1. A pharmaceutical composition for use in a method for treating psoriatic arthritis comprising the anti-IL-23p19 antibody hum13B8-b, wherein the antibody hum13B8-b is (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1; (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2; wherein the method comprises administering to a patient in need thereof an initial dose of the antibody subcutaneously at week 0, followed by subsequent doses subcutaneously over a period of up to 72 hours every 12 weeks thereafter for at least 24 weeks; and wherein said treatment results in at least a 20% improvement from baseline in tender and swollen joint counts. Pharmaceutical compositions.

17. 17. The pharmaceutical composition of claim 16, wherein the treatment further results in at least a 20% improvement from baseline in at least three of five parameters selected from the group consisting of: (i) physician global assessment of disease activity, (ii) patient global assessment of disease activity, (iii) patient pain assessment, (iv) patient self-rated disability, and (v) acute CRP.

18. 1. A pharmaceutical composition for use in a method for treating psoriatic arthritis comprising the anti-IL-23p19 antibody hum13B8-b, wherein the antibody hum13B8-b is (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1; (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2; wherein the method comprises administering to a patient in need thereof an initial dose of the antibody subcutaneously at week 0, followed by subsequent doses subcutaneously over a period of up to 72 hours every 12 weeks thereafter for at least 24 weeks; and wherein said treatment results in at least a 50% improvement from baseline in tender and swollen joint counts. Pharmaceutical compositions.

19. 19. The pharmaceutical composition of claim 18, wherein the treatment further results in at least a 50% improvement from baseline in at least three of five parameters selected from the group consisting of: (i) physician global assessment of disease activity, (ii) patient global assessment of disease activity, (iii) patient pain assessment, (iv) patient self-rated disability, and (v) acute CRP.

20. 1. A pharmaceutical composition for use in a method for treating psoriatic arthritis comprising the anti-IL-23p19 antibody hum13B8-b, wherein the antibody hum13B8-b is (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1; (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2; wherein the method comprises administering to a patient in need thereof an initial dose of the antibody subcutaneously at week 0, followed by subsequent doses subcutaneously over a period of up to 72 hours every 12 weeks thereafter for at least 24 weeks; and wherein said treatment results in at least a 70% improvement from baseline in tender and swollen joint counts. Pharmaceutical compositions.

21. 21. The pharmaceutical composition of claim 20, wherein the treatment further results in at least a 70% improvement from baseline in at least three of five parameters selected from the group consisting of: (i) physician global assessment of disease activity, (ii) patient global assessment of disease activity, (iii) patient pain assessment, (iv) patient self-rated disability, and (v) acute CRP.

22. 1. A composition for use in a method for determining the efficacy of an anti-IL-23p19 antibody for treating psoriatic arthritis, comprising: wherein the composition comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1; (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2; wherein said method comprises administering to said patient an initial dose of antibody hum13B8-b subcutaneously at week 0, and subsequent doses of antibody hum13B8-b subcutaneously every 12 weeks for up to 72 hours following said initial dose for at least 24 weeks; and wherein An ACR20 response rate of at least about 40% at week 24 or week 52 indicates efficacy of the antibody. composition.

23. 23. The composition of claim 22, wherein an ACR20 response value of at least about 50% at week 24 or week 52 indicates efficacy of the antibody.

24. 23. The composition of claim 22, wherein an ACR20 response value of at least about 60% at week 24 or week 52 indicates efficacy of the antibody.

25. 1. A composition for use in a method for determining the efficacy of an anti-IL-23p19 antibody for treating psoriatic arthritis, comprising: wherein the composition comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1; (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2; wherein said method comprises administering to a patient an initial dose of said antibody subcutaneously at week 0, and subsequent doses every 12 weeks for up to 72 hours following said initial dose, for at least 24 weeks; and wherein An ACR50 response rate of at least about 20% at week 24 or week 52 indicates efficacy of the antibody. composition.

26. 26. The composition of claim 25, wherein an ACR50 response value of at least about 25% at week 24 or week 52 indicates efficacy of the antibody.

27. 26. The composition of claim 25, wherein an ACR50 response value of at least about 30% at week 24 or week 52 indicates efficacy of the antibody.

28. 1. A composition for use in a method for determining the efficacy of an anti-IL-23p19 antibody for treating psoriatic arthritis, comprising: wherein the composition comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1; (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2; wherein said method comprises administering to a patient an initial dose of said antibody subcutaneously at week 0, and subsequent doses every 12 weeks for up to 72 hours following said initial dose, for at least 24 weeks; and wherein An ACR70 response rate of at least 10% at week 24 or week 52 indicates efficacy of the antibody. composition.

29. 30. The composition of claim 28, wherein an ACR50 response value of at least about 12% at week 24 or week 52 indicates efficacy of the antibody.

30. 30. The composition of claim 28, wherein an ACR50 response value of at least about 15% at week 24 or week 52 indicates efficacy of the antibody.

31. The composition of any one of claims 22 to 30, wherein the initial dose and the subsequent dose are the same.

32. The composition of any one of claims 22 to 30, wherein the initial dose and the subsequent doses are different.

33. The composition of any one of claims 22 to 30, wherein the initial dose is 100 mg.

34. The composition of any one of claims 22 to 30, wherein the initial dose is 200 mg.

35. The composition of any one of claims 22 to 30, wherein the subsequent dose is 100 mg.

36. The composition of any one of claims 22 to 30, wherein the subsequent dose is 200 mg.

37. The composition of any one of claims 22 to 30, wherein the initial dose and the subsequent doses are 100 mg.

38. The composition of any one of claims 22 to 30, wherein the initial dose and the subsequent doses are 200 mg.

39. 1. A composition for use in a method for determining the efficacy of an anti-IL-23p19 antibody for treating psoriatic arthritis, comprising: wherein the composition comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1; (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2; wherein said method comprises administering to a patient an initial dose of said antibody subcutaneously at week 0, followed by subsequent doses every 12 weeks over a period of up to 72 hours for at least 24 weeks; and wherein At least a 75% improvement from baseline in psoriasis area and severity index at week 52 indicates efficacy of the anti-IL-23p19 antibody. composition.

40. 40. The composition of claim 39, wherein an improvement of at least 90% from baseline in Psoriasis Area and Severity Index at week 52 indicates efficacy of the antibody.

41. 40. The composition of claim 39, wherein an improvement of at least 100% from baseline in Psoriasis Area and Severity Index at week 52 indicates efficacy of the antibody.

42. 1. A composition for use in a method for determining the efficacy of an anti-IL-23p19 antibody for treating psoriatic arthritis, comprising: The composition comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1; (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2; wherein said method comprises administering to a patient an initial dose of said antibody subcutaneously at week 0, followed by subsequent doses every 12 weeks over a period of up to 72 hours for at least 24 weeks; and wherein A decrease in DAS28-CRP score from baseline at week 52 indicates efficacy of the antibody. composition.

43. 1. A composition for use in a method for determining the efficacy of an anti-IL-23p19 antibody for treating psoriatic arthritis, comprising administering to a patient the anti-IL-23p19 antibody hum13B8-b, wherein the antibody hum13B8-b is (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:1; (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:2; wherein said method comprises administering to a patient an initial dose of said antibody subcutaneously at week 0, followed by subsequent doses every 12 weeks over a period of up to 72 hours for at least 24 weeks; and wherein A statistically significant improvement in disease activity at week 52 as determined by minimal disease activity (MDA) criteria indicates efficacy of the antibody. composition.

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