Ruxolitinib preparation for reducing itchiness in atopic dermatitis

Abstract

To provide a method for treating atopic dermatitis, and a method for reducing itchiness of a patient having atopic dermatitis.SOLUTION: A method for reducing itchiness of a human patient having atopic dermatitis includes administering a cream preparation to the skin of the human patient who needs the cream preparation twice a day, where the cream preparation contains ruxolitinib or a pharmaceutically acceptable salt thereof by 1.5% (w / w) on the basis of a free base, the patient achieves statistically significant reduction of an itchiness numerical evaluation scale score from a baseline within 36 hours of administration.SELECTED DRAWING: None

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 62 / 896,421, filed September 5, 2019, U.S. Provisional Application No. 62 / 897,059, filed September 6, 2019, U.S. Provisional Application No. 62 / 898,873, filed September 11, 2019, U.S. Provisional Application No. 62 / 983,252, filed February 28, 2020, and U.S. Provisional Application No. 63 / 020,668, filed May 6, 2020. Each of these applications is incorporated herein by reference in its entirety.

[0002] The present disclosure relates to methods of reducing itch in patients with atopic dermatitis, and methods of treating patients with atopic dermatitis by administering topical ruxolitinib cream, including 0.75% or 1.5% ruxolitinib cream, twice daily. [Background technology]

[0003] Atopic dermatitis affects approximately 10% of adults (Silverberg JI, Hanifin JM. J Allergy Clin Immunol 2013;132:1132-1138), is increasing in incidence, and costs $3.8 billion annually in direct medical costs alone (Ellis CN, et al. J Am Acad Dermatol 2002;46:361-370). According to a recent Global Burden of Disease project, atopic dermatitis ("Atopic dermatitis, AD"), one of the 50 most prevalent diseases in the world, has the second highest disability ranking among all non-malignant skin diseases (Hay RJ, et al. J Invest Dermatol 2014;134:1527-1534). Despite the advances in multiple targeted biological treatments for psoriasis, only one such treatment currently exists for AD (Dupixent®).

[0004] One of the main features and diagnostic criteria of AD is pruritus (itching). Itching leads to scratching, which can further damage AD skin, exacerbate the disease, and cause secondary infections. Furthermore, nighttime itching and scratching can result in loss of sleep and reduced quality of life for patients and their close relatives, e.g., parents of a child with AD.

[0005] Topical therapy for AD is limited to topical steroids, topical calcineurin inhibitors, and more recently PDE4 inhibitors (Eucrisa®). These drugs all have limitations related to efficacy levels, safety (especially with long-term use), or tolerability issues. The use of topical steroids may also be associated with irreversible side effects such as skin atrophy and linear atrophy of the skin. The use of systemic glucocorticoids and calcineurin inhibitors is also limited due to their adverse event (AE) profile. When current topical therapies fail, systemic immunosuppressants (e.g., cyclosporine, methotrexate) are occasionally used, with highly variable efficacy and / or a high risk of AEs.

[0006] Importantly, none of the currently available drugs have a direct effect on relieving itch. Thus, new approaches are needed to rapidly and effectively control itch in AD patients. As mentioned above, itch is a major feature of AD and a symptom that directly contributes to the high disease (quality of life) burden in this condition. The present disclosure addresses this and other needs. Summary of the Invention

[0007] The present disclosure provides, inter alia, methods of using ruxolitinib to reduce itch in human patients with atopic dermatitis and to treat human patients with atopic dermatitis. Ruxolitinib is a potent JAK1 / JAK2 inhibitor, (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile (INCB018424; ruxolitinib; the active ingredient in JAKAFI®), and pharma- ceutically acceptable salts thereof, previously described in U.S. Patent No. 7,598,257, which is incorporated herein by reference in its entirety. Ruxolitinib phosphate has previously been described in U.S. Patent Publication No. 2008 / 0312259, which is incorporated herein by reference in its entirety. [ka]

[0008] For example, a method for treating atopic dermatitis in a human patient is provided, the method comprising administering to the skin of a human patient in need thereof a cream formulation comprising ruxolitinib or a pharma- ceutically acceptable salt thereof. In another example, a method for reducing itch in a human patient having atopic dermatitis is provided, the method comprising administering to the skin of a human patient in need thereof a cream formulation comprising ruxolitinib or a pharma- ceutically acceptable salt thereof, wherein the patient achieves a reduction in itch numerical rating scale score from baseline.

[0009] The present disclosure also provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering twice daily to the skin of said human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis; Here, the patient achieves a reduction in itch numerical rating scale score from baseline.

[0010] The disclosure also provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) of ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis; Here, the patient achieves a reduction in itch numerical rating scale score from baseline.

[0011] The present disclosure further provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering twice daily (BID) to the skin of said human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis; Here, the patient achieves a reduction in itch numerical rating scale score from baseline.

[0012] The present disclosure also provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering twice daily (BID) to the skin of said human patient in need thereof a cream formulation comprising 0.75% (w / w) ruxolitinib phosphate on a free base basis; Here, the patient achieves a reduction in itch numerical rating scale score from baseline.

[0013] The present disclosure also provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering twice daily to the skin of said human patient in need thereof a cream formulation comprising 0.75% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis; Here, the patient achieves a reduction in itch numerical rating scale score from baseline.

[0014] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0015] The present disclosure also provides a method of treating atopic dermatitis in a human patient, comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) ruxolitinib phosphate on a free base basis. The present disclosure also provides a method of relieving itch in a human patient having atopic dermatitis, comprising administering twice daily to the skin of said human patient in need thereof a cream formulation, wherein said cream formulation is an oil-in-water emulsion comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis; wherein administration is maintained for at least 8 weeks (e.g., 12 weeks, etc.); Patients achieve at least a 4 point reduction in Itch Numeric Rating Scale score from baseline at week 8 of treatment.

[0016] The present disclosure also provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering a cream formulation twice daily to the skin of the human patient in need thereof, the cream formulation being an oil-in-water emulsion comprising 0.75% (w / w) ruxolitinib phosphate on a free base basis; wherein administration is maintained for at least 8 weeks (e.g., 12 weeks, etc.); Patients achieve at least a 4 point reduction in Itch Numeric Rating Scale score from baseline at week 8 of treatment.

[0017] The present disclosure further provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering a cream formulation twice daily to the skin of the human patient in need thereof, the cream formulation being an oil-in-water emulsion containing 1.5% (w / w) ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; The patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of said administration; and The patient: Between 18 and 70 years old, Have been diagnosed with atopic dermatitis for at least 2 years Investigator Global Assessment score was 2-3 at screening and baseline; and 3% to 20% of the body surface area (excluding face and interstitial areas) involved in atopic dermatitis at baseline.

[0018] The present disclosure further provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering a cream formulation twice daily to the skin of the human patient in need thereof, the cream formulation being an oil-in-water emulsion containing 0.75% (w / w) or 1.5% (w / w) of ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; The patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of said administration; and The patient: You are a young person between the ages of 12 and 17, or a man or woman aged 18 or over, have a history of AD for at least 2 years; Investigator's Global Assessment score of 2-3 at baseline, and %BSA of AD involvement excluding scalp was 3% to 20% at baseline.

[0019] The present disclosure also provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering a cream formulation twice daily to the skin of the human patient in need thereof, the cream formulation being an oil-in-water emulsion comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; The patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of said administration; and Patients will achieve an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of treatment.

[0020] The present disclosure also provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering a cream formulation twice daily to the skin of the human patient in need thereof, the cream formulation being an oil-in-water emulsion comprising 0.75% (w / w) ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; The patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of said administration; and Patients will achieve an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of treatment.

[0021] The present disclosure further provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering a cream formulation twice daily to the skin of the human patient in need thereof, the cream formulation being an oil-in-water emulsion containing 1.5% (w / w) ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; the patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of said administration; The patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of dosing; and The patient: Between 18 and 70 years old, Have been diagnosed with atopic dermatitis for at least 2 years Investigator Global Assessment score was 2-3 at screening and baseline; and 3% to 20% of the body surface area (excluding face and interstitial areas) involved in atopic dermatitis at baseline.

[0022] The present disclosure further provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering a cream formulation twice daily to the skin of the human patient in need thereof, the cream formulation being an oil-in-water emulsion containing 0.75% (w / w) or 1.5% (w / w) of ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; the patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of said administration; The patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of dosing; and The patient: You are a young person between the ages of 12 and 17, or a man or woman aged 18 or over, have a history of AD for at least 2 years; Investigator Global Assessment score was 2-3 at baseline; %BSA of AD involvement excluding scalp was 3% to 20% at baseline.

[0023] The disclosure also provides a method of treating moderate atopic dermatitis in a human patient in need thereof, comprising administering a topical formulation twice daily to the skin of said human patient, wherein said topical formulation comprises 0.75% (w / w) or 1.5% (w / w) of ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis.

[0024] The disclosure also provides a method of treating moderate to severe atopic dermatitis in a human patient in need thereof, comprising administering twice daily to the skin of said human patient, wherein said topical formulation comprises 0.75% (w / w) or 1.5% (w / w) of ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis.

[0025] The present disclosure also provides a method of treating atopic dermatitis in a human patient in need thereof, comprising administering twice daily to the skin of said human patient, said topical formulation comprising 0.75% (w / w) or 1.5% (w / w) of ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis; wherein the patient has a baseline Eczema Area and Severity Index score of 16 or greater; and ≥10% of body surface area involved in atopic dermatitis at baseline.

[0026] The present disclosure further provides a topical formulation (e.g., a cream formulation) comprising 0.75% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis, for use in any of the methods described herein.

[0027] The present disclosure also provides a topical formulation (e.g., a cream formulation) comprising 1.5% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis, for use in any of the methods described herein.

[0028] The disclosure further provides the use of a topical formulation (e.g., a cream formulation) comprising 0.75% (w / w) ruxolitinib, or a pharma- ceutically acceptable salt thereof, on a free base basis, in the manufacture of a medicament for use in any of the methods described herein.

[0029] The disclosure further provides the use of a topical formulation (e.g., a cream formulation) comprising 1.5% (w / w) ruxolitinib, or a pharma- ceutically acceptable salt thereof, on a free base basis, in the manufacture of a medicament for use in any of the methods described herein.

[0030] In the figure, "RUX" is ruxolitinib phosphate. In the figure, "TAC" is triamcinolone. [Brief description of the drawings]

[0031] [Figure 1]Graphs of mean percent improvement from baseline in EASI score for vehicle (BID), triamcinolone (0.1% BID), and ruxolitinib cream (0.15% QD, 0.5% QD, 1.5% QD, and 1.5% BID) at weeks 2 (first bar of each set), 4 (second bar of each set), and 8 (third bar of each set). 0.1% TAC does not display a bar because TAC was only administered for 4 weeks. [Diagram 2] Graphs of mean percent improvement from baseline in EASI score for vehicle (BID), triamcinolone (0.1% BID), and ruxolitinib cream (1.5% BID) at weeks 2 (first bar of each set), 4 (second bar of each set), and 8 (third bar of each set). 0.1% TAC does not display a bar because TAC was only administered for 4 weeks. [Diagram 3] Graphs of percentage of EASI-75 responders (at least 75% improvement in EASI from baseline) for vehicle (BID), triamcinolone (0.1% BID), and ruxolitinib cream (0.15% QD, 0.5% QD, 1.5% QD, and 1.5% BID) at weeks 2 (first bar of each set), 4 (second bar of each set), and 8 (third bar of each set). 0.1% TAC does not display a bar because TAC was only administered for 4 weeks. [Figure 4] Graphs of the percentage of IGA responses (responders were patients who achieved an IGA score of 0-1 with ≥2 point improvement from baseline) for vehicle (BID), triamcinolone (0.1% BID), and ruxolitinib cream (0.15% QD, 0.5% QD, 1.5% QD, and 1.5% BID) at weeks 2 (first graph bar in each set), 4 (second graph bar in each set), and 8 (third graph bar in each set). 0.1% TAC does not show a bar because TAC was only administered for 4 weeks. [Diagram 5]Graph of mean percent improvement from baseline in EASI score for vehicle, triamcinolone, and ruxolitinib cream over 12 weeks. The open-label period was from week 8 to week 12, and 1.5% ruxolitinib cream was administered. [Figure 6]

[0033] Figure 1 shows the percentage of IGA responses for vehicle, triamcinolone, and ruxolitinib cream over 12 weeks. The open-label period was from week 8 to week 12, when 1.5% ruxolitinib cream was administered. [Figure 7] FIG. 1 is a graph of the mean change from baseline in daily itch NRS scores (NRS scores range from 0 to 10, with 0 being no itch and 10 being the worst itch possible) for vehicle (BID), triamcinolone (0.1% BID), and ruxolitinib cream (0.15% QD, 0.5% QD, 1.5% QD, and 1.5% BID) over a 28-day period. [Figure 8] 1 is a graph of the mean change from baseline in daily itch NRS scores for vehicle (BID), triamcinolone (0.1% BID), and ruxolitinib cream (1.5% BID) over a 28 day period. [Figure 9] Graph of mean itch NRS scores for vehicle, triamcinolone, and ruxolitinib cream over 12 weeks. The open-label period was from week 8 to week 12, when 1.5% ruxolitinib cream was administered. [Figure 10] Graphs of mean percent improvement from baseline in Skindex-16 global score for vehicle (BID), triamcinolone (0.1% BID), and ruxolitinib cream (0.15% QD, 0.5% QD, 1.5% QD, and 1.5% BID) at weeks 2 (first bar in each set), 4 (second bar in each set), and 8 (third bar in each set). 0.1% TAC does not display a bar because TAC was administered for only 4 weeks. ** indicates P<0.01 vs. vehicle, *** indicates P<0.001 vs. vehicle. † indicates that the TAC arm received 0.1% TAC cream until week 4, then vehicle. [Figure 11] FIG. 1 shows the percentage of participants who achieved IGA-TS during the week 2, 4, and 8 vehicle control periods for TRuE-AD1 (Study 303) (solid bars) and TRuE-AD2 (Study 304) (striped bars) for vehicle, 0.75% BID ruxolitinib cream, and 1.5% BID ruxolitinib cream (the first bar in each set is vehicle, the second bar in each set is 0.75% BID ruxolitinib cream, and the third bar in each set is 1.5% ruxolitinib cream). [Figure 12] FIG. 1 shows the percentage of participants who achieved EASI75 during the week 2, 4, and 8 vehicle control periods for TRuE-AD1 (Study 303) (solid bars) and TRuE-AD2 (Study 304) (striped bars) for vehicle, 0.75% BID ruxolitinib cream, and 1.5% BID ruxolitinib cream (the first bar in each set is vehicle, the second bar in each set is 0.75% BID ruxolitinib cream, and the third bar in each set is 1.5% ruxolitinib cream). [Figure 13] FIG. 1 shows the percentage of participants who achieved an improvement of 4 or more points in Itch NRS score during the vehicle control period at weeks 2, 4, and 8 for TRuE-AD1 (Study 303) (solid bars) and TRuE-AD2 (Study 304) (striped bars) for vehicle, 0.75% BID ruxolitinib cream, and 1.5% BID ruxolitinib cream (the first bar in each set is vehicle, the second bar in each set is 0.75% BID ruxolitinib cream, and the third bar in each set is 1.5% ruxolitinib cream) among patients with a baseline Itch NRS score ≥ 4. [Figure 14] FIG. 1 shows the mean change from baseline in daily itch NRS scores from Day 1 to Day 28 of TRuE-AD1 (Study 303) for vehicle (top line), 0.75% BID ruxolitinib cream (middle line), and 1.5% BID ruxolitinib cream (bottom line) in patients with a baseline itch NRS score ≧4. [Figure 15]FIG. 1 shows the mean change from baseline in daily itch NRS scores from Days 1 to 28 of TRuE-AD2 (Study 304) for vehicle (top line), 0.75% BID ruxolitinib cream (middle line), and 1.5% BID ruxolitinib cream (bottom line) in patients with a baseline itch NRS score ≧4. [Figure 16] FIG. 1 shows the percentage of participants who achieved a 6-point or greater improvement in the PROMIS sleep disorder score (8b) during weeks 2, 4, and 8 of the vehicle-controlled period for TRuE-AD1 (Study 303) (solid bars) and TRuE-AD2 (Study 304) (striped bars) for vehicle, 0.75% BID ruxolitinib cream, and 1.5% BID ruxolitinib cream (the first bar in each set is vehicle, the second bar in each set is 0.75% BID ruxolitinib cream, and the third bar in each set is 1.5% ruxolitinib cream). [Figure 17] FIG. 1 shows the percentage of participants who achieved a 6-point or greater improvement in the PROMIS sleep disorder score (8a) during weeks 2, 4, and 8 of the vehicle-controlled period for TRuE-AD1 (Study 303) (solid bars) and TRuE-AD2 (Study 304) (striped bars) for vehicle, 0.75% BID ruxolitinib cream, and 1.5% BID ruxolitinib cream (the first bar in each set is vehicle, the second bar in each set is 0.75% BID ruxolitinib cream, and the third bar in each set is 1.5% ruxolitinib cream). [Figure 18] FIG. 13 shows box plots of hemoglobin (g / L) change from baseline at weeks 2, 4, and 8 of the vehicle control period in TRuE-AD1 (Study 303) for vehicle, 0.75% BID ruxolitinib cream, and 1.5% BID ruxolitinib cream (the first bar in each set is vehicle, the second bar in each set is 0.75% BID ruxolitinib cream, and the third bar in each set is 1.5% ruxolitinib cream). [Figure 19]FIG. 13 shows box plots of change from baseline in platelets (109 / L) during weeks 2, 4, and 8 of the vehicle control period in TRuE-AD1 (Study 303) for vehicle, 0.75% BID ruxolitinib cream, and 1.5% BID ruxolitinib cream (the first bar in each set is vehicle, the second bar in each set is 0.75% BID ruxolitinib cream, and the third bar in each set is 1.5% ruxolitinib cream). [Figure 20] FIG. 13 shows box plots of hemoglobin (g / L) change from baseline during the vehicle control period at weeks 2, 4, and 8 of TRuE-AD2 (Study 304) for vehicle, 0.75% BID ruxolitinib cream, and 1.5% BID ruxolitinib cream (the first bar in each set is vehicle, the second bar in each set is 0.75% BID ruxolitinib cream, and the third bar in each set is 1.5% ruxolitinib cream). [Figure 21] FIG. 13 shows box plots of change from baseline in platelets (109 / L) during weeks 2, 4, and 8 of the vehicle control period in TRuE-AD2 (Study 304) for vehicle, 0.75% BID ruxolitinib cream, and 1.5% BID ruxolitinib cream (the first bar in each set is vehicle, the second bar in each set is 0.75% BID ruxolitinib cream, and the third bar in each set is 1.5% ruxolitinib cream). [Figure 22] FIG. 1 shows the percentage of participants who achieved IGA-TS during the week 2, 4, and 8 vehicle control periods for both TRuE-AD1 (Study 303) and TRuE-AD2 (Study 304) for vehicle, 0.75% BID ruxolitinib cream, and 1.5% BID ruxolitinib cream (the first bar in each set is vehicle, the second bar in each set is 0.75% BID ruxolitinib cream, and the third bar in each set is 1.5% ruxolitinib cream) in patients with ≥10% body surface area involved by atopic dermatitis at baseline and a baseline Eczema Area and Severity Index score ≥16. [Figure 23]FIG. 1 shows the percentage of participants who achieved EASI-75 during the week 2, 4, and 8 vehicle control periods for both TRuE-AD1 (Study 303) and TRuE-AD2 (Study 304) for vehicle, 0.75% BID ruxolitinib cream, and 1.5% BID ruxolitinib cream (the first bar in each set is vehicle, the second bar in each set is 0.75% BID ruxolitinib cream, and the third bar in each set is 1.5% ruxolitinib cream) in patients with ≥10% body surface area involved by atopic dermatitis at baseline and a baseline Eczema Area and Severity Index score ≥16. [Figure 24] FIG. 1 shows the percentage of participants who achieved an improvement in Itch NRS score of 4 points or more during the vehicle control periods at weeks 2, 4, and 8 for both TRuE-AD1 (Study 303) and TRuE-AD2 (Study 304) for vehicle, 0.75% BID ruxolitinib cream, and 1.5% BID ruxolitinib cream (the first bar in each set is vehicle, the second bar in each set is 0.75% BID ruxolitinib cream, and the third bar in each set is 1.5% ruxolitinib cream) in patients with an Itch NRS of 4 or more at baseline for patients with atopic dermatitis involved body surface area ≥ 10% at baseline, an Eczema Area and Severity Index score ≥ 16 at baseline, and an Itch Numeric Rating Scale score ≥ 4 at baseline. [Diagram 25] FIG. 1 shows the mean change from baseline in daily itch NRS scores from Day 1 through Day 28 for pooled TRuE-AD1 (Study 303) and TRuE-AD2 (Study 304) studies (top line (vehicle), mid line (0.75% BID ruxolitinib cream), and bottom line (1.5% BID ruxolitinib cream)) (for patients with a baseline itch NRS score ≥ 4). [Figure 26]FIG. 1 shows the proportion of patients (of patients with baseline Itch NRS score ≥ 4) who achieved a ≥ 4 point improvement in Itch NRS score from Day 1 to Day 7 for pooled TRuE-AD1 (Study 303) and TRuE-AD2 (Study 304) studies (1st bar (vehicle), 2nd bar (0.75% BID ruxolitinib cream), and 3rd bar (1.5% BID ruxolitinib cream)). [Figure 27] FIG. 1 shows the percentage of participants who achieved IGA-TS during the vehicle-controlled periods at weeks 2, 4, and 8 of pooled TRuE-AD1 (Study 303) and TRuE-AD2 (Study 304) studies for vehicle, 0.75% BID ruxolitinib cream, and 1.5% BID ruxolitinib cream (the first bar in each set is vehicle, the second bar in each set is 0.75% BID ruxolitinib cream, and the third bar in each set is 1.5% ruxolitinib cream). [Figure 28] FIG. 1 shows the percentage of participants who achieved EASI-75 during the vehicle control periods at weeks 2, 4, and 8 of pooled TRuE-AD1 (Study 303) and TRuE-AD2 (Study 304) for vehicle, 0.75% BID ruxolitinib cream, and 1.5% BID ruxolitinib cream (the first bar in each set is vehicle, the second bar in each set is 0.75% BID ruxolitinib cream, and the third bar in each set is 1.5% ruxolitinib cream). [Figure 29] FIG. 1 shows the percentage of participants who achieved a 6-point improvement in PROMIS sleep disorder score (8b) or greater during the vehicle-controlled periods at weeks 2, 4, and 8 of pooled TRuE-AD1 (Study 303) and TRuE-AD2 (Study 304) for vehicle, 0.75% BID ruxolitinib cream, and 1.5% BID ruxolitinib cream (1st bar in each set is vehicle, 2nd bar in each set is 0.75% BID ruxolitinib cream, 3rd bar in each set is 1.5% ruxolitinib cream) among patients with a PROMIS sleep disorder score (8b) ≥ 6 at baseline. [Diagram 30] FIG. 1 shows the percentage of participants who achieved a 6-point improvement or greater in PROMIS Sleep-Related Disorders (8a) during the vehicle-controlled periods at weeks 2, 4, and 8 of pooled TRuE-AD1 (Study 303) and TRuE-AD2 (Study 304) for vehicle, 0.75% BID ruxolitinib cream, and 1.5% BID ruxolitinib cream (first bar in each set is vehicle, second bar in each set is 0.75% BID ruxolitinib cream, third bar in each set is 1.5% ruxolitinib cream) among patients with a PROMIS Sleep-Related Disorders (8a) ≥ 6 at baseline. [Diagram 31] FIG. 1 shows a graph of the mean EASI scores at baseline, week 2, week 4, and week 8 vehicle control periods for pooled TRuE-AD1 (Study 303) and TRuE-AD2 (Study 304) (top line (vehicle)), mid line (0.75% BID ruxolitinib cream), and bottom line (1.5% BID ruxolitinib cream). [Diagram 32] FIG. 1 shows a graph of the mean score change from baseline in EASI scores during the vehicle control period at baseline, week 2, week 4, and week 8 for pooled TRuE-AD1 (Study 303) and TRuE-AD2 (Study 304) (top line (vehicle)), mid line (1.5% BID ruxolitinib cream), and bottom line (0.75% BID ruxolitinib cream). [Diagram 33] FIG. 1 shows a graph of the mean percentage change from baseline in EASI scores at baseline, week 2, week 4, and week 8 of the vehicle control period for pooled TRuE-AD1 (Study 303) and TRuE-AD2 (Study 304) (top line (vehicle)), mid line (1.5% BID ruxolitinib cream), and bottom line (0.75% BID ruxolitinib cream). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0032] The present disclosure provides, inter alia, a method for relieving itch in a human patient having atopic dermatitis, the method comprising administering twice daily to the skin of said human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis; Here, the patient achieves a reduction in itch numerical rating scale score from baseline.

[0033] The disclosure also provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) of ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis; Here, the patient achieves a reduction in itch numerical rating scale score from baseline.

[0034] The disclosure further provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering twice daily to the skin of said human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis; Here, the patient achieves a reduction in itch numerical rating scale score from baseline.

[0035] The present disclosure further provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering twice daily (BID) to the skin of said human patient in need thereof a cream formulation comprising 0.75% (w / w) ruxolitinib phosphate on a free base basis; Here, the patient achieves a reduction in itch numerical rating scale score from baseline.

[0036] In some embodiments, the method provides rapid relief to the patient from itching.

[0037] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) or 1.5% (w / w) of ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis.

[0038] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0039] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis.

[0040] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0041] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering a cream formulation comprising 0.75% (w / w) ruxolitinib phosphate on a free base basis to the skin of a human patient in need thereof twice daily.

[0042] In some embodiments, the ruxolitinib, or a pharma- ceutically acceptable salt thereof, is ruxolitinib phosphate.

[0043] In some embodiments, patients achieve an Investigator's Global Assessment score of 0 or 1 with at least a 2 point improvement from baseline.

[0044] In some embodiments, the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline.

[0045] The disclosure also provides a method of treating mild to moderate atopic dermatitis in a human patient in need thereof, comprising administering a topical formulation twice daily to the skin of said human patient, wherein said topical formulation comprises 0.75% (w / w) or 1.5% (w / w) of ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis.

[0046] The disclosure also provides a method of treating mild to moderate atopic dermatitis in a human patient in need thereof, comprising administering a topical formulation twice daily to the skin of said human patient, wherein said topical formulation comprises 0.75% (w / w) ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis.

[0047] The disclosure also provides a method of treating mild to moderate atopic dermatitis in a human patient in need thereof, comprising administering a topical formulation twice daily to the skin of said human patient, wherein said topical formulation comprises 1.5% (w / w) ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis.

[0048] The present disclosure also provides a method of treating mild to moderate atopic dermatitis in a human patient in need thereof, comprising administering a topical formulation twice daily to the skin of the human patient, wherein the topical formulation comprises 0.75% (w / w) ruxolitinib phosphate on a free base basis.

[0049] The present disclosure also provides a method of treating mild to moderate atopic dermatitis in a human patient in need thereof, comprising administering a topical formulation twice daily to the skin of the human patient, wherein the topical formulation comprises 1.5% (w / w) ruxolitinib phosphate on a free base basis.

[0050] The present disclosure also provides a method of treating mild to moderate atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) or 1.5% (w / w) of ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0051] The present disclosure also provides a method of treating mild to moderate atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0052] The present disclosure also provides a method of treating mild to moderate atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0053] The present disclosure also provides a method of treating mild to moderate atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) ruxolitinib phosphate on a free base basis.

[0054] The present disclosure also provides a method of treating mild to moderate atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis.

[0055] The disclosure also provides a method of treating moderate atopic dermatitis in a human patient in need thereof, comprising administering a topical formulation twice daily to the skin of said human patient, wherein said topical formulation comprises 0.75% (w / w) or 1.5% (w / w) of ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis.

[0056] The disclosure also provides a method of treating moderate atopic dermatitis in a human patient in need thereof, comprising administering a topical formulation twice daily to the skin of said human patient, wherein said topical formulation comprises 0.75% (w / w) ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis.

[0057] The disclosure also provides a method of treating moderate atopic dermatitis in a human patient in need thereof, comprising administering a topical formulation twice daily to the skin of said human patient, wherein said topical formulation comprises 1.5% (w / w) ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis.

[0058] The present disclosure also provides a method of treating moderate atopic dermatitis in a human patient in need thereof, comprising administering a topical formulation twice daily to the skin of the human patient, wherein the topical formulation comprises 0.75% (w / w) ruxolitinib phosphate on a free base basis.

[0059] The present disclosure also provides a method of treating moderate atopic dermatitis in a human patient in need thereof, comprising administering a topical formulation twice daily to the skin of the human patient, wherein the topical formulation comprises 1.5% (w / w) ruxolitinib phosphate on a free base basis.

[0060] The present disclosure also provides a method of treating moderate atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) or 1.5% (w / w) of ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis.

[0061] The present disclosure also provides a method of treating moderate atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis.

[0062] The present disclosure also provides a method of treating moderate atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis.

[0063] The present disclosure also provides a method of treating moderate atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) ruxolitinib phosphate on a free base basis.

[0064] The present disclosure also provides a method of treating moderate atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis.

[0065] The disclosure also provides a method of treating moderate to severe atopic dermatitis in a human patient in need thereof, comprising administering twice daily to the skin of said human patient, wherein said topical formulation comprises 0.75% (w / w) or 1.5% (w / w) of ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis.

[0066] The disclosure also provides a method of treating moderate to severe atopic dermatitis in a human patient in need thereof, comprising administering twice daily to the skin of said human patient, wherein said topical formulation comprises 0.75% (w / w) ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis.

[0067] The disclosure also provides a method of treating moderate to severe atopic dermatitis in a human patient in need thereof, comprising administering a topical formulation twice daily to the skin of said human patient, wherein said topical formulation comprises 1.5% (w / w) ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis.

[0068] The present disclosure also provides a method of treating moderate to severe atopic dermatitis in a human patient in need thereof, comprising administering a topical formulation twice daily to the skin of the human patient, wherein the topical formulation comprises 0.75% (w / w) ruxolitinib phosphate on a free base basis.

[0069] The present disclosure also provides a method of treating moderate to severe atopic dermatitis in a human patient in need thereof, comprising administering a topical formulation twice daily to the skin of the human patient, wherein the topical formulation comprises 1.5% (w / w) ruxolitinib phosphate on a free base basis.

[0070] The present disclosure also provides a method of treating moderate to severe atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) or 1.5% (w / w) of ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis.

[0071] The present disclosure also provides a method of treating moderate to severe atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0072] The present disclosure also provides a method of treating moderate to severe atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0073] The present disclosure also provides a method of treating moderate to severe atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) ruxolitinib phosphate on a free base basis.

[0074] The present disclosure also provides a method of treating moderate to severe atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis.

[0075] In some embodiments of the embodiment of the previous 20 paragraphs, the patient achieves a reduction in the Itch Numeric Rating Scale score of at least 4 points from baseline. In some embodiments of the embodiment of the previous 20 paragraphs, the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2 point improvement from baseline. In some embodiments of the embodiment of the previous 20 paragraphs, the patient achieves a statistically significant improvement in the Eczema Area and Severity Index score from baseline. In some embodiments of the embodiment of the previous 20 paragraphs, the patient achieves a 75% improvement in the Eczema Area and Severity Index score from baseline. In some embodiments of the embodiment of the previous 20 paragraphs, the patient achieves a reduction in the Itch Numeric Rating Scale score of at least 4 points from baseline and the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2 point improvement from baseline. In some embodiments of the embodiment of the previous 20 paragraphs, the patient achieves a reduction in the Itch Numeric Rating Scale score of at least 4 points from baseline and the patient achieves a 75% improvement in the Eczema Area and Severity Index score from baseline. In some embodiments of the embodiment of the previous 20 paragraphs, the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2 point improvement from baseline, and the patient achieves a 75% improvement from baseline in the Eczema Area and Severity Index score. In some embodiments of the embodiment of the previous 20 paragraphs, the patient reduces the Itch Numeric Rating Scale score by at least 4 points from baseline, the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2 point improvement from baseline, and the patient achieves a 75% improvement from baseline in the Eczema Area and Severity Index score. In some embodiments of the embodiment of the previous 20 paragraphs, the patient reduces the Itch Numeric Rating Scale score by at least 4 points from baseline at week 4 of said administration. In some embodiments of the embodiment of the previous 20 paragraphs, the patient reduces the Itch Numeric Rating Scale score by at least 4 points from baseline at week 8 of said administration.In some embodiments of the embodiment of the previous 20 paragraphs, the patient achieves an Investigator's Global Assessment score of 0 or 1 at week 4 of said administration, with at least a 2 point improvement from baseline. In some embodiments of the embodiment of the previous 20 paragraphs, the patient achieves an Investigator's Global Assessment score of 0 or 1 at week 8 of said administration, with at least a 2 point improvement from baseline. In some embodiments of the embodiment of the previous 20 paragraphs, the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 4 of said administration. In some embodiments of the embodiment of the previous 20 paragraphs, the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 8 of said administration. In some embodiments of the embodiment of the previous 20 paragraphs, the patient achieves a reduction in Itch Numeric Rating Scale score of at least 4 points from baseline at week 4 of said administration, and the patient achieves an Investigator's Global Assessment score of 0 or 1 at week 4 of said administration, with at least a 2 point improvement from baseline. In some embodiments of the embodiment of the previous 20 paragraphs, the patient achieves a reduction in the Itch Numeric Rating Scale score of at least 4 points from baseline at week 8 of said administration, and the patient achieves an Investigator's Global Assessment score of 0 or 1, with at least a 2 point improvement from baseline at week 8 of said administration. In some embodiments of the embodiment of the previous 20 paragraphs, the patient achieves a reduction in the Itch Numeric Rating Scale score of at least 4 points from baseline at week 4 of said administration, and the patient achieves a 75% improvement in the Eczema Area and Severity Index score from baseline at week 4 of said administration. In some embodiments of the embodiment of the previous 20 paragraphs, the patient achieves a reduction in the Itch Numeric Rating Scale score of at least 4 points from baseline at week 8 of said administration, and the patient achieves a 75% improvement in the Eczema Area and Severity Index score from baseline at week 8 of said administration. In some embodiments of the embodiment of the previous 20 paragraphs, the patient achieves an Investigator's Global Assessment score of 0 or 1 at week 4 of said administration, with at least a 2 point improvement from baseline, and the patient achieves a 75% improvement from baseline in Eczema Area and Severity Index score at week 4 of said administration.In some embodiments of the embodiment of the previous 20 paragraphs, the patient achieves an Investigator's Global Assessment score of 0 or 1 at week 8 of said dosing, with at least a 2 point improvement from baseline, and the patient achieves a 75% improvement from baseline in an Eczema Area and Severity Index score at week 8 of said dosing. In some embodiments of the embodiment of the previous 20 paragraphs, the patient achieves a reduction in an Itch Numeric Rating Scale score of at least 4 points from baseline at week 4 of said dosing, the patient achieves an Investigator's Global Assessment score of 0 or 1 at week 4 of said dosing, with at least a 2 point improvement from baseline, and the patient achieves a 75% improvement from baseline in an Eczema Area and Severity Index score at week 4 of said dosing. In some embodiments of the embodiment of the previous 20 paragraphs, the patient achieves at least a 4 point reduction in Itch Numeric Rating Scale score from baseline at week 8 of said administration, the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2 point improvement from baseline at week 8 of said administration, and the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 8 of said administration. In some embodiments of the embodiment of the previous 20 paragraphs, administration is maintained for at least 4 weeks. In some embodiments of the embodiment of the previous 20 paragraphs, administration is maintained for at least 8 weeks.

[0076] In general, mild-to-moderate, moderate, and moderate-to-severe atopic dermatitis are defined by the FDA, i.e., by the Investigator's Global Assessment score at baseline (see IGA definitions above). For example, a patient with mild atopic dermatitis has a baseline Investigator's Global Assessment score of 2. A patient with moderate atopic dermatitis has a baseline Investigator's Global Assessment score of 3, and a patient with severe atopic dermatitis has a baseline Investigator's Global Assessment score of 4. A patient with mild-to-moderate atopic dermatitis has a baseline Investigator's Global Assessment score of 2-3, and a patient with moderate-to-severe atopic dermatitis has a baseline Investigator's Global Assessment score of 3-4.

[0077] In some embodiments, patients with mild to moderate atopic dermatitis have 10% or more of their body surface area involved in atopic dermatitis at baseline. In some embodiments, patients with moderate atopic dermatitis have 10% or more of their body surface area involved in atopic dermatitis at baseline. In some embodiments, patients with moderate to severe atopic dermatitis have 10% or more of their body surface area involved in atopic dermatitis at baseline.

[0078] In some embodiments, patients with mild to moderate atopic dermatitis have 10% to 20% of their body surface area involved in atopic dermatitis at baseline. In some embodiments, patients with moderate atopic dermatitis have 10% to 20% of their body surface area involved in atopic dermatitis at baseline. In some embodiments, patients with moderate to severe atopic dermatitis have 10% to 20% of their body surface area involved in atopic dermatitis at baseline.

[0079] In some embodiments, patients with moderate atopic dermatitis have a baseline Eczema Area and Severity Index of 16 or greater. In some embodiments, patients with moderate to severe atopic dermatitis have a baseline Eczema Area and Severity Index of 16 or greater.

[0080] In some embodiments, patients with moderate atopic dermatitis have an Investigator's Global Assessment score of 3 and 10% to 20% of their body surface area involved by atopic dermatitis at baseline.

[0081] In some embodiments, patients with moderate to severe atopic dermatitis have an Eczema Area and Severity Index of 16 or greater at baseline, 10% or more of their body surface area involved by atopic dermatitis at baseline, and an Investigator's Global Assessment score of 3-4.

[0082] The disclosure further provides a method of treating atopic dermatitis in a human patient in need thereof, comprising administering twice daily to the skin of said human patient, said topical formulation comprising 0.75% (w / w) or 1.5% (w / w) of ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis; wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater, and ≥10% of body surface area involved in atopic dermatitis at baseline.

[0083] The disclosure further provides a method of treating atopic dermatitis in a human patient in need thereof, comprising administering twice daily to the skin of said human patient, said topical formulation comprising 0.75% (w / w) ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis; wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater, and ≥10% of body surface area involved in atopic dermatitis at baseline.

[0084] The disclosure further provides a method of treating atopic dermatitis in a human patient in need thereof, comprising administering twice daily to the skin of said human patient, said topical formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis; wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater, and ≥10% of body surface area involved in atopic dermatitis at baseline.

[0085] The present disclosure also provides a method of treating atopic dermatitis in a human patient in need thereof, comprising administering a topical formulation twice daily to the skin of the human patient, wherein the topical formulation comprises 0.75% (w / w) ruxolitinib phosphate on a free base basis; wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater, and ≥10% of body surface area involved in atopic dermatitis at baseline.

[0086] The present disclosure also provides a method of treating atopic dermatitis in a human patient in need thereof, comprising administering a topical formulation twice daily to the skin of the human patient, wherein the topical formulation comprises 1.5% (w / w) ruxolitinib phosphate on a free base basis; wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater, and ≥10% of body surface area involved in atopic dermatitis at baseline.

[0087] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) or 1.5% (w / w) of ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis; wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater, and ≥10% of body surface area involved in atopic dermatitis at baseline.

[0088] The disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis; wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater, and ≥10% of body surface area involved in atopic dermatitis at baseline.

[0089] The disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis; wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater, and ≥10% of body surface area involved in atopic dermatitis at baseline.

[0090] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) ruxolitinib phosphate on a free base basis; wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater, and ≥10% of body surface area involved in atopic dermatitis at baseline.

[0091] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis; wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater, and ≥10% of body surface area involved in atopic dermatitis at baseline.

[0092] In some embodiments of the embodiment of the previous 10 paragraphs, the patient has a baseline Investigator's Global Assessment score of 3. In some embodiments of the embodiment of the previous 10 paragraphs, the patient has a baseline Investigator's Global Assessment score of 3 to 4. In some embodiments of the embodiment of the previous 10 paragraphs, the patient has a baseline Itch Numeric Rating Scale score of 4 or greater. In some embodiments of the embodiment of the previous 10 paragraphs, the patient has a baseline Investigator's Global Assessment score of 3 and a baseline Itch Numeric Rating Scale score of 4 or greater. In some embodiments of the embodiment of the previous 10 paragraphs, the patient has a baseline Investigator's Global Assessment score of 3 to 4 and a baseline Itch Numeric Rating Scale score of 4 or greater. In some embodiments of the embodiment of the previous 10 paragraphs, the patient is 12 years of age or older. In some embodiments of the embodiment of the previous 10 paragraphs, the patient has a history of atopic dermatitis for at least 2 years. In some embodiments of the embodiment of the previous 10 paragraphs, the patient has a baseline Investigator's Global Assessment score of 3, a history of atopic dermatitis for at least 2 years, and is 12 years of age or older. In some embodiments of the embodiment of the previous 10 paragraphs, the patient has a baseline Investigator's Global Assessment score of 3-4, a history of atopic dermatitis for at least 2 years, and is 12 years of age or older. In some embodiments of the embodiment of the previous 10 paragraphs, the patient has a baseline Investigator's Global Assessment score of 3, a baseline Numeric Itch Rating Scale score of 4 or greater, a history of atopic dermatitis for at least 2 years, and is 12 years of age or older. In some embodiments of the embodiment of the previous 10 paragraphs, the patient has a baseline Investigator's Global Assessment score of 3-4, a baseline Numeric Itch Rating Scale score of 4 or greater, a history of atopic dermatitis for at least 2 years, and is 12 years of age or older.In some embodiments of the embodiment of the previous 10 paragraphs, the patient has one or more of the following characteristics: an Investigator's Global Assessment score of 3 at baseline, an Itch Numeric Rating Scale score of 4 or greater at baseline, a history of atopic dermatitis for at least 2 years, and age 12 or greater. In some embodiments of the embodiment of the previous 10 paragraphs, the patient achieves a reduction in Itch Numeric Rating Scale score of at least 4 points from baseline. In some embodiments of the embodiment of the previous 10 paragraphs, the patient achieves an Investigator's Global Assessment score of 0 or 1, with at least a 2 point improvement from baseline. In some embodiments of the embodiment of the previous 10 paragraphs, the patient achieves a statistically significant improvement in Eczema Area and Severity Index score from baseline. In some embodiments of the embodiment of the previous 10 paragraphs, the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline. In some embodiments of the embodiment of the previous 10 paragraphs, the patient achieves a reduction in the Itch Numeric Rating Scale score of at least 4 points from baseline, and the patient achieves an Investigator's Global Assessment score of 0 or 1, with at least a 2 point improvement from baseline. In some embodiments of the embodiment of the previous 10 paragraphs, the patient achieves a reduction in the Itch Numeric Rating Scale score of at least 4 points from baseline, and the patient achieves a 75% improvement from baseline in the Eczema Area and Severity Index score. In some embodiments of the embodiment of the previous 10 paragraphs, the patient achieves an Investigator's Global Assessment score of 0 or 1, with at least a 2 point improvement from baseline, and the patient achieves a 75% improvement from baseline in the Eczema Area and Severity Index score. In some embodiments of the embodiment of the previous 10 paragraphs, the patient achieves a reduction in the Itch Numeric Rating Scale score of at least 4 points from baseline, the patient achieves an Investigator's Global Assessment score of 0 or 1, with at least a 2 point improvement from baseline, and the patient achieves a 75% improvement from baseline in the Eczema Area and Severity Index score.In some embodiments of the embodiment of the previous 10 paragraphs, the patient achieves at least a 4 point reduction in Itch Numeric Rating Scale score from baseline at week 4 of said administration. In some embodiments of the embodiment of the previous 10 paragraphs, the patient achieves at least a 4 point reduction in Itch Numeric Rating Scale score from baseline at week 8 of said administration. In some embodiments of the embodiment of the previous 10 paragraphs, the patient achieves an Investigator's Global Assessment score of 0 or 1 at week 4 of said administration, with at least a 2 point improvement from baseline. In some embodiments of the embodiment of the previous 10 paragraphs, the patient achieves at least a 2 point improvement from baseline in an Investigator's Global Assessment score of 0 or 1 at week 8 of said administration. In some embodiments of the embodiment of the previous 10 paragraphs, the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 4 of said administration. In some embodiments of the embodiment of the previous 10 paragraphs, the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 8 of said administration. In some embodiments of the embodiment of the previous 10 paragraphs, the patient achieves a reduction in the Itch Numeric Rating Scale score from baseline at week 4 of said administration, and the patient achieves an Investigator's Global Assessment score of 0 or 1, with at least a 2 point improvement from baseline at week 4 of said administration. In some embodiments of the embodiment of the previous 10 paragraphs, the patient achieves a reduction in the Itch Numeric Rating Scale score from baseline at week 8 of said administration, and the patient achieves an Investigator's Global Assessment score of 0 or 1, with at least a 2 point improvement from baseline at week 8 of said administration. In some embodiments of the embodiment of the previous 10 paragraphs, the patient achieves a reduction in the Itch Numeric Rating Scale score from baseline at week 4 of said administration, and the patient achieves a 75% improvement from baseline in the Eczema Area and Severity Index score at week 4 of said administration.In some embodiments of the embodiment of the previous 10 paragraphs, the patient achieves at least a 4 point reduction in Itch Numeric Rating Scale score from baseline at week 8 of said administration, and the patient achieves a 75% improvement from baseline in Eczema Area and Severity Index score at week 8 of said administration. In some embodiments of the embodiment of the previous 10 paragraphs, the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2 point improvement from baseline at week 4 of said administration, and the patient achieves a 75% improvement from baseline in Eczema Area and Severity Index score at week 4 of said administration. In some embodiments of the embodiment of the previous 10 paragraphs, the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2 point improvement from baseline at week 8 of said administration, and the patient achieves a 75% improvement from baseline in Eczema Area and Severity Index score at week 8 of said administration. In some embodiments of the embodiment of the previous 10 paragraphs, the patient reduces the Itch Numeric Rating Scale score by at least 4 points from baseline at week 4 of said administration, the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2 point improvement from baseline at week 4 of said administration, and the patient achieves a 75% improvement from baseline in the Eczema Area and Severity Index score at week 4 of said administration. In some embodiments of the embodiment of the previous 10 paragraphs, the patient reduces the Itch Numeric Rating Scale score by at least 4 points from baseline at week 8 of said administration, the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2 point improvement from baseline at week 8 of said administration, and the patient achieves a 75% improvement from baseline in the Eczema Area and Severity Index score at week 8 of said administration. In some embodiments of the embodiment of the previous 10 paragraphs, administration is maintained for at least 4 weeks. In some embodiments of the embodiment of the previous 10 paragraphs, administration is maintained for at least 8 weeks.

[0093] In some embodiments, the topical formulation is a cream formulation. In some embodiments, the ruxolitinib or its salt is ruxolitinib phosphate. In some embodiments, the formulation comprises ruxolitinib or its pharmaceutically acceptable salt at 0.75% (w / w) based on the free base. In some embodiments, the formulation comprises ruxolitinib or its pharmaceutically acceptable salt at 1.5% (w / w) based on the free base. In some embodiments, the formulation comprises ruxolitinib or its pharmaceutically acceptable salt at 0.75% (w / w) based on the free base. In some embodiments, the formulation comprises ruxolitinib phosphate at 1.5% (w / w) based on the free base.

[0094] In some embodiments, the patient achieves at least a 4-point improvement in improvement in itch numeric rating scale score from baseline. In some embodiments, the patient achieves at least a 4-point improvement in improvement in itch numeric rating scale score from baseline, where the patient has a baseline numeric rating scale score of 4 or more. In some embodiments, the patient achieves at least a 4-point improvement in improvement in itch numeric rating scale score from baseline 2 weeks after said administration, where the patient has a baseline numeric rating scale score of 4 or more. In some embodiments, the patient achieves at least a 4-point improvement in improvement in itch numeric rating scale score from baseline 4 weeks after said administration, where the patient has a baseline numeric rating scale score of 4 or more. In some embodiments, the patient achieves at least a 4-point improvement in improvement in itch numeric rating scale score from baseline 8 weeks after said administration, where the patient has a baseline numeric rating scale score of 4 or more.

[0095] In some embodiments, the patient is Between 18 and 70 years old, Have been diagnosed with atopic dermatitis for at least 2 years Investigator Global Assessment score was 2-3 at screening and baseline; and 3% to 20% of the body surface area (excluding face and interstitial areas) involved in atopic dermatitis at baseline.

[0096] In some embodiments, the patient is You are a young person between the ages of 12 and 17, or a man or woman aged 18 or over, have a history of AD for at least 2 years; Investigator Global Assessment score was 2-3 at baseline; %BSA of AD involvement excluding scalp was 3% to 20% at baseline.

[0097] In some embodiments, the patient is You are a young person between the ages of 12 and 17, or a man or woman aged 18 or over, have a history of AD for at least 2 years; Investigator Global Assessment score was 2-3 at baseline; %BSA of AD involvement excluding scalp was between 3% and 20% at baseline; Approximately 10 cm at baseline 2 Have at least one target lesion (representing the participant's medical condition and not on the hands, feet, or genitals) listed above.

[0098] In some embodiments, the patient is diagnosed with atopic dermatitis as defined by the Hanifin and Rajka criteria.

[0099] In some embodiments, the patient did not use any topical treatments for atopic dermatitis, other than emollients, within 2 weeks of baseline.

[0100] In some embodiments, patients have not used systemic immunosuppressants or immunomodulatory agents (e.g., oral or injectable corticosteroids, methotrexate, cyclosporine, mycophenolate mofetil, or azathioprine) within 4 weeks or 5 half-lives (whichever is longer) from baseline.

[0101] In some embodiments, patients have not used topical treatments for atopic dermatitis other than mild emollients within 2 weeks of baseline, and have not used systemic immunosuppressants or systemic immunomodulatory drugs within 4 weeks of baseline.

[0102] In some embodiments, the patient is not receiving other therapeutic agents used to treat atopic dermatitis.

[0103] In some embodiments, the patient is not receiving systemic immunosuppressants or systemic immunomodulators, or topical treatments for atopic dermatitis other than a mild emollient.

[0104] In some embodiments, the patient is (i) no evidence of active acute or chronic infection; (ii) no use of topical treatment for atopic dermatitis (except mild emollients) within 2 weeks of baseline; (iii) no use of systemic immunosuppressants or immunomodulatory drugs (e.g., oral or injectable corticosteroids, methotrexate, cyclosporine, mycophenolate mofetil, or azathioprine) within 4 weeks or 5 half-lives (whichever is longer) of baseline; (iv) no diagnosis of other skin diseases other than atopic dermatitis whose presence or treatment might complicate the evaluation of disease; (v) history of other diseases other than skin diseases receiving treatment that might complicate the evaluation; (vi) white blood cell count <3.0 × 10 at screening. 9(vii) did not have cytopenias, defined as ≥ 1.5 mg / dL, neutrophils < lower limit of normal, hemoglobin < 10 g / dL, lymphocytes < 0.8 × 109 / L, platelets < 100 × 109 / L; (viii) did not have severe liver dysfunction (Child-Pugh class C) or end-stage renal disease on dialysis or at least one of the following: serum creatinine > 1.5 mg / dL, alanine aminotransferase or aspartate aminotransferase ≥ 1.5 × upper limit of normal; (viii) had not taken a potent systemic cytochrome P450 3A4 inhibitor or fluconazole within 2 weeks or 5 half-lives, whichever was longer, prior to the baseline visit, except for topical agents with limited systemic availability; and / or (ix) did not receive a systemic or topical Janus kinase inhibitor.

[0105] In some embodiments, the patient is (i) Adolescents aged 12 to 17 years, or males or females aged 18 years or older; (ii) diagnosed with AD as defined by the Hanifin and Rajka criteria; (iii) have a medical history of AD for at least 2 years; (iv) have an Investigator's Global Assessment score of 2 to 3 at baseline; (v) have %BSA of AD involvement excluding scalp of 3% to 20% at baseline; (vi) have agreed to discontinue all medications used to treat AD during treatment; and / or (vi) have a mean of ≥ 10 cm at baseline. 2 Have at least one target lesion (representing the participant's medical condition and not present on the hands, feet, or genitals) of size ≥ 10 cm.

[0106] In some embodiments, the patient is (i) Absence of an unstable course of AD (spontaneously improving or rapidly worsening) as determined by a physician in the 4 weeks prior to baseline; (ii) Concomitant symptoms and history of other diseases: (a) immunodeficiency (e.g., lymphoma, acquired immune deficiency syndrome, Wiskott-Aldrich syndrome); (b) chronic or acute infection requiring treatment with systemic antibiotics, antivirals, anthelmintics, antiprotozoals, or antifungals within 2 weeks prior to baseline; (c) active acute bacterial, fungal, or viral skin infection within 1 week prior to baseline (e.g., herpes simplex, shingles, chickenpox); (d) other concomitant skin disorders (e.g., generalized erythroderma such as Netherton syndrome), hyperpigmentation, or extensive scarring) that, in the investigator's opinion, could interfere with the assessment of AD lesions or compromise the participant's safety; (e) AD lesions present only on the hands or feet with no history of involvement of other areas of early involvement such as the face or folds; (f) absence of other types of eczema. (iii) Free of any serious illness or medical, physical, or psychiatric condition that, in the opinion of the Investigator, may prevent full participation in the study, including administration of the study drug and participation in necessary study visits, pose a significant risk to the participant, or interfere with interpretation of the study data. For example, (a) unless approved by the Medical Monitor / Sponsor, clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months of Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, and arrhythmias or uncontrolled hypertension (blood pressure >150 / 90 mmHg) requiring treatment; (b) Participants with a history of malignancy within 5 years prior to enrollment in this study, except for adequately treated non-metastatic malignancies; (c) low hemoglobin (<10 g / dL); (d) severe renal disease on dialysis (serum creatinine >2 mg / dL); (e) current and / or history of liver disease, including known hepatitis B or C, with liver or bile duct abnormalities.(iv) not receiving any of the following treatments within the indicated washout period prior to baseline: (a) 5 half-lives or 12 weeks, whichever is longer—biological agents (e.g., dupilumab); (b) 4 weeks—systemic corticosteroids or adrenocorticotropic hormone analogs, cyclosporine, methotrexate, azathioprine, or other systemic immunosuppressants or immunomodulators (e.g., mycophenolate or tacrolimus); (c) 2 weeks—immunization and sedating antihistamines (nonsedating antihistamines are permitted) unless on a long-term stable regimen; (d) 1 week—use of other topical treatments for AD (except mild emollients), such as corticosteroids, calcineurin inhibitors, coal tar (shampoo), antibiotics, or antibacterial cleansing body washes / soaps. Diluted sodium hypochlorite "bleach" baths are permitted as long as they do not exceed 2 baths per week, the frequency of which is the same throughout the study. (v) Have not previously received a systemic or topical JAK inhibitor; (vi) Have not received ultraviolet light therapy or prolonged exposure to natural or artificial sources of UV radiation (e.g., sunlight or tanning booths) within 2 weeks prior to baseline, and / or have no intention of undergoing such exposure during the study that the Investigator believes may affect the participant's AD; (vii) Have no positive serological test results screening for HIV antibodies; (viii) Have no of the following liver function tests: AST or ALT ≥ 2 × ULN; alkaline phosphatase and / or bilirubin > 1.5 × ULN (isolated bilirubin > 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin is < 35%); (ix) Are not pregnant, breastfeeding, or considering pregnancy; (x) Have no history of alcoholism or drug dependence within 1 year prior to screening or current alcohol or drug use that, in the Investigator's opinion, would interfere with the participant's ability to comply with the dosing schedule and study assessments. and / or (xi) not currently receiving treatment or have not received treatment within 30 days or 5 half-lives (whichever is longer) prior to baseline with another investigational drug, or have no current enrollment in another investigational drug protocol.

[0107] In some embodiments, the two daily doses are at least 8 hours apart.

[0108] In some embodiments, the cream formulation is an oil-in-water emulsion comprising the ruxolitinib, or a pharma- ceutically acceptable salt thereof.

[0109] In some embodiments, the cream formulation is an oil-in-water emulsion containing 1.5% (w / w) ruxolitinib phosphate on a free base basis.

[0110] In some embodiments, the cream formulation is an oil-in-water emulsion containing 0.75% (w / w) ruxolitinib phosphate on a free base basis.

[0111] In some embodiments, the cream formulation has a pH of about 2.8 to about 3.9.

[0112] In some embodiments, the cream formulation has a pH of about 2.8 to about 3.6.

[0113] In some embodiments, the cream formulation is a solubilized cream.

[0114] In some embodiments, administration of the cream formulation does not result in a statistically significant decrease in hemoglobin or platelets. In some embodiments, administration of the cream formulation does not result in burning at the administration site. In some embodiments, administration of the cream formulation does not result in itching at the administration site.

[0115] In some embodiments, the patient achieves rapid relief from the itch.

[0116] In some embodiments, the patient achieves a statistically significant reduction in itch on the first day (i.e., within 12 hours) of said administration. In some embodiments, the patient achieves a statistically significant reduction in itch on the first day (i.e., within 12 hours) of said administration of a cream formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof.

[0117] In some embodiments, patients achieve a statistically significant reduction in itch numerical rating scale score from baseline on the second day of said administration compared to patients administered a placebo for the same period of time.

[0118] In some embodiments, patients achieve a statistically significant reduction in itch numerical rating scale score from baseline on day 1 of said administration compared to patients administered a placebo for the same period of time.

[0119] In some embodiments, the patient achieves at least a 1 point reduction in itch numerical rating scale score from baseline on the first day of said administration.

[0120] In some embodiments, the patient achieves at least a 2 point improvement in Itch Numeric Rating Scale score improvement from baseline on the first day of said administration.

[0121] In some embodiments, the patient achieves at least a 1.5 point reduction in itch numerical rating scale score from baseline on the first day of said administration.

[0122] In some embodiments, the patient achieves at least a 1 point reduction in itch numerical rating scale score from baseline on the second day of said administration.

[0123] In some embodiments, the patient achieves at least a 1.5 point reduction in itch numerical rating scale score from baseline on the second day of said administration.

[0124] In some embodiments, the patient achieves at least a 2 point reduction in itch numerical rating scale score from baseline on the second day of said administration.

[0125] In some embodiments, the patient achieves at least a 2 point reduction in itch numerical rating scale score from baseline on the fourth day of said administration.

[0126] In some embodiments, the patient achieves at least a 1 point reduction in the Itch Numeric Rating Scale score by the second day of said administration.

[0127] In some embodiments, the patient achieves at least a 1 point reduction in the Itch Numeric Rating Scale score within 36 hours of said administration.

[0128] In some embodiments, the patient achieves at least a 2 point reduction in the Itch Numeric Rating Scale score by day 6 of said administration.

[0129] In some embodiments, the patient achieves at least a 2 point reduction in the Itch Numeric Rating Scale score during the first week of said administration.

[0130] In some embodiments, the patient achieves at least a 3 point reduction in the Itch Numeric Rating Scale score at the third week of said administration.

[0131] In some embodiments, the patient achieves at least a 1 point reduction in the itch numeric rating scale score by the second day of said administration, at least a 2 point reduction in the itch numeric rating scale score by the sixth day of said administration, and at least a 3 point reduction in the itch numeric rating scale score by the third week of said administration.

[0132] In some embodiments, the patient achieves at least a 1 point reduction in the Itch Numeric Rating Scale score within 36 hours of said administration, at least a 2 point reduction in the Itch Numeric Rating Scale score by the 6th day of said administration, and at least a 3 point reduction in the Itch Numeric Rating Scale score by the 3rd week of said administration.

[0133] In some embodiments, the patient achieves at least a 1 point reduction in the itch numeric rating scale score by the second day of said administration, at least a 2 point reduction in the itch numeric rating scale score by the first week of said administration, and at least a 3 point reduction in the itch numeric rating scale score by the third week of said administration.

[0134] In some embodiments, the patient achieves at least a 1 point reduction in itch numeric rating scale score within 36 hours of said administration, at least a 2 point reduction in itch numeric rating scale score within the first week of said administration, and at least a 3 point reduction in itch numeric rating scale score within the third week of said administration.

[0135] A method for reducing itch in a human patient having atopic dermatitis, comprising administering twice daily to the skin of said human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis, wherein said patient achieves at least a 1 point reduction in itch numerical rating scale score by the second day of said administration.

[0136] A method for reducing itch in a human patient having atopic dermatitis, comprising administering twice daily to the skin of the human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis, wherein the patient achieves at least a 1 point reduction in itch numerical rating scale score within 36 hours of said administration.

[0137] A method for reducing itch in a human patient having atopic dermatitis, comprising administering twice daily to the skin of said human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis, wherein said patient achieves a reduction in itch numerical rating scale score of at least 2 points by the sixth day of said administration.

[0138] A method for relieving itch in a human patient having atopic dermatitis, comprising administering twice daily to the skin of the human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis, wherein the patient achieves a reduction in itch numerical rating scale score of at least 2 points during the first week of said administration.

[0139] A method for reducing itch in a human patient having atopic dermatitis, comprising administering twice daily to the skin of the human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis, wherein the patient achieves a reduction in itch numerical rating scale score of at least 3 points during the third week of said administration.

[0140] A method of reducing itch in a human patient having atopic dermatitis, comprising administering twice daily to the skin of the human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis, wherein the patient achieves at least a 1 point reduction in itch numerical rating scale score by the second day of said administration, at least a 2 point reduction in itch numerical rating scale score by the sixth day of said administration, and at least a 3 point reduction in itch numerical rating scale score by the third week of said administration.

[0141] 1. A method of reducing itch in a human patient having atopic dermatitis, comprising administering twice daily to the skin of the human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis, wherein the patient achieves at least a 1 point reduction in itch numerical rating scale score within 36 hours of said administration, at least a 2 point reduction in itch numerical rating scale score by the 6th day of said administration, and at least a 3 point reduction in itch numerical rating scale score by the 3rd week of said administration.

[0142] A method of reducing itch in a human patient having atopic dermatitis, comprising administering twice daily to the skin of the human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis, wherein the patient achieves at least a 1 point reduction in itch numerical rating scale score by the second day of said administration, at least a 2 point reduction in itch numerical rating scale score during the first week of said administration, and at least a 3 point reduction in itch numerical rating scale score during the third week of said administration.

[0143] 1. A method of reducing itch in a human patient having atopic dermatitis, comprising administering twice daily to the skin of the human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis, wherein the patient achieves at least a 1 point reduction in itch numerical rating scale score within 36 hours of said administration, at least a 2 point reduction in itch numerical rating scale score during the first week of said administration, and at least a 3 point reduction in itch numerical rating scale score during the third week of said administration.

[0144] In some embodiments, the patient achieves a minimal clinically important difference in itch numerical rating scale score on the first day of said administration.

[0145] In some embodiments, the patient achieves a minimal clinically important difference in itch numerical rating scale score on the second day of said administration.

[0146] In some embodiments, the patient achieves a minimal clinically important difference in itch numerical rating scale score on the third day of said administration.

[0147] In some embodiments, the patient achieves a minimal clinically important difference in itch numerical rating scale score on the fourth day of said administration.

[0148] In some embodiments, the patient achieves a clinically relevant improvement in Itch Numeric Rating Scale score on the second day of said administration.

[0149] In some embodiments, the patient achieves a clinically relevant improvement in Itch Numeric Rating Scale score on the third day of said administration.

[0150] In some embodiments, the patient achieves a clinically relevant improvement in Itch Numeric Rating Scale score on the fourth day of said administration.

[0151] In some embodiments, patients achieve a statistically significant reduction in itch numerical rating scale score from baseline during the second week of said administration compared to patients administered a placebo for the same period.

[0152] In some embodiments, the patient achieves at least a 3 point reduction in Itch Numeric Rating Scale score from baseline during the second week of said administration.

[0153] In some embodiments, the patient achieves a clinically relevant improvement in Itch Numeric Rating Scale score at the second week of said administration.

[0154] In some embodiments, patients achieve a statistically significant reduction in itch numeric rating scale score from baseline at week 4 of said administration compared to patients administered a placebo for the same period.

[0155] In some embodiments, the patient achieves at least a 3 point reduction in Itch Numeric Rating Scale score from baseline at week 4 of said administration.

[0156] In some embodiments, the patient achieves a clinically relevant improvement in Itch Numeric Rating Scale score at week 4 of said administration.

[0157] In some embodiments, patients achieve a statistically significant reduction in itch numerical rating scale score from baseline at week 8 of said administration compared to patients administered a placebo for the same period.

[0158] In some embodiments, the patient achieves at least a 3 point reduction in Itch Numeric Rating Scale score from baseline at week 8 of said administration.

[0159] In some embodiments, the patient achieves at least a 4 point reduction in Itch Numeric Rating Scale score from baseline at week 8 of said administration.

[0160] In some embodiments, the patient achieves a clinically relevant improvement in Itch Numeric Rating Scale score at week 8 of said administration.

[0161] In some embodiments, the patient achieves at least a 4.5 point reduction in Itch Numeric Rating Scale score from baseline at week 12 of said administration.

[0162] In some embodiments, the administration reverses the symptoms of atopic dermatitis.

[0163] In some embodiments, patients achieve a statistically significant improvement in Eczema Area and Severity Index scores from baseline at week 4 of said administration compared to patients administered a placebo for the same period.

[0164] In some embodiments, patients achieve a statistically significant improvement in Eczema Area and Severity Index score from baseline at week 8 of said administration compared to patients administered a placebo for the same period.

[0165] In some embodiments, the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at the second week of said administration.

[0166] In some embodiments, the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 4 of said administration.

[0167] In some embodiments, the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 8 of said administration.

[0168] In some embodiments, the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 12 of said administration.

[0169] In some embodiments, the patient achieves an Investigator's Global Assessment score of 0 or 1, with at least a 2 point improvement from baseline, at week 2 of said administration.

[0170] In some embodiments, the patient achieves an Investigator's Global Assessment score of 0 or 1, with at least a 2 point improvement from baseline, at week 4 of said administration.

[0171] In some embodiments, the patient achieves an Investigator's Global Assessment score of 0 or 1, with at least a 2 point improvement from baseline, at week 8 of said administration.

[0172] In some embodiments, patients achieve a clinically meaningful improvement in the PROMIS Short Form-Sleep Disorders (8b) 24-hour recall score at Week 8.

[0173] In some embodiments, the patient achieves at least a 50% improvement in Skindex-16 global score at the second week of said administration.

[0174] In some embodiments, the patient achieves at least a 60% improvement in Skindex-16 global score at the second week of said administration.

[0175] In some embodiments, the patient achieves at least a 50% improvement in Skindex-16 global score at week 4 of said administration.

[0176] In some embodiments, the patient achieves at least a 60% improvement in Skindex-16 global score at week 4 of said administration.

[0177] In some embodiments, the patient achieves at least a 70% improvement in Skindex-16 global score at week 4 of said administration.

[0178] In some embodiments, the patient achieves at least a 50% improvement in Skindex-16 global score at week 8 of said administration.

[0179] In some embodiments, the patient achieves at least a 60% improvement in Skindex-16 global score at week 8 of said administration.

[0180] In some embodiments, the patient achieves at least a 70% improvement in Skindex-16 global score at week 8 of said administration.

[0181] In some embodiments, the patient suffers from mild to moderate atopic dermatitis.

[0182] In some embodiments, the administration is maintained for at least two weeks.

[0183] In some embodiments, administration is maintained for at least 4 weeks.

[0184] In some embodiments, administration is maintained for at least 8 weeks.

[0185] In some embodiments, administration is maintained for at least 12 weeks.

[0186] The present disclosure also provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering a cream formulation twice daily to the skin of the human patient in need thereof, the cream formulation being an oil-in-water emulsion comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; Patients achieve at least a 4 point reduction in Itch Numeric Rating Scale score from baseline at week 8 of treatment.

[0187] The present disclosure further provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering a cream formulation twice daily to the skin of the human patient in need thereof, the cream formulation being an oil-in-water emulsion containing 0.75% (w / w) ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; Patients achieve at least a 4 point reduction in Itch Numeric Rating Scale score from baseline at week 8 of treatment.

[0188] The present disclosure also provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering a cream formulation twice daily to the skin of the human patient in need thereof, the cream formulation being an oil-in-water emulsion comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; Patients achieved at least a 4-point reduction in itch numeric rating scale score from baseline at week 8 of treatment, The patient: Between 18 and 70 years old, Have been diagnosed with atopic dermatitis for at least 2 years Investigator Global Assessment score was 2-3 at screening and baseline; and 3% to 20% of the body surface area (excluding face and interstitial areas) involved in atopic dermatitis at baseline.

[0189] The present disclosure further provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering a cream formulation twice daily to the skin of the human patient in need thereof, the cream formulation being an oil-in-water emulsion containing 0.75% (w / w) or 1.5% (w / w) of ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; Patients achieved at least a 4-point reduction in itch numeric rating scale score from baseline at week 8 of treatment, The patient: You are a young person between the ages of 12 and 17, or a man or woman aged 18 or over, have a history of AD for at least 2 years; Investigator Global Assessment score was 2-3 at baseline; %BSA of AD involvement excluding scalp was 3% to 20% at baseline.

[0190] The present disclosure also provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering a cream formulation twice daily to the skin of the human patient in need thereof, the cream formulation being an oil-in-water emulsion comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; The patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of said administration; and Patients will achieve an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of treatment.

[0191] The present disclosure also provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering a cream formulation twice daily to the skin of the human patient in need thereof, the cream formulation being an oil-in-water emulsion containing 0.75% (w / w) or 1.5% (w / w) of ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; The patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of said administration; and Patients will achieve an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of treatment.

[0192] The present disclosure further provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering a cream formulation twice daily to the skin of the human patient in need thereof, the cream formulation being an oil-in-water emulsion containing 1.5% (w / w) ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; the patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of said administration; The patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of dosing; and The patient: Between 18 and 70 years old, Have been diagnosed with atopic dermatitis for at least 2 years Investigator Global Assessment score was 2-3 at screening and baseline; and 3% to 20% of the body surface area (excluding face and interstitial areas) involved in atopic dermatitis at baseline.

[0193] The present disclosure further provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering a cream formulation twice daily to the skin of the human patient in need thereof, the cream formulation being an oil-in-water emulsion containing 0.75% (w / w) or 1.5% (w / w) of ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; the patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of said administration; The patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of dosing; and The patient: You are a young person between the ages of 12 and 17, or a man or woman aged 18 or over, have a history of AD for at least 2 years; Investigator Global Assessment score was 2-3 at baseline; %BSA of AD involvement excluding scalp was 3% to 20% at baseline.

[0194] In another embodiment, the present disclosure provides a method of reducing itch in a human patient having atopic dermatitis, the method comprising: (1) 1.5% (w / w) ruxolitinib phosphate on a free base basis, (2) a means for effecting dose-dependent skin penetration of the ruxolitinib phosphate, said composition comprising said ruxolitinib phosphate and said ...

[0195] In another embodiment, the present disclosure provides a method of reducing itch in a human patient having atopic dermatitis, the method comprising: (1) 0.75% (w / w) ruxolitinib phosphate on a free base basis, (2) a means for effecting dose-dependent skin penetration of the ruxolitinib phosphate, said composition comprising said ruxolitinib phosphate and said ...

[0196] The present disclosure also provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering twice daily to the skin of said human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis; Here, the patient achieves a reduction in itch numerical rating scale score from baseline.

[0197] The disclosure also provides a method of relieving itch in a human patient having atopic dermatitis, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) of ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis; Here, the patient achieves a reduction in itch numerical rating scale score from baseline.

[0198] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) or 1.5% (w / w) of ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis; wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater; Having ≥10% of the body surface area involved in atopic dermatitis at baseline A baseline itch numeric rating scale score of 4 or greater; and have one or more characteristics selected from the group consisting of an Investigator's Global Assessment score of at least 3 at baseline.

[0199] The disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis; wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater; Having ≥10% of the body surface area involved in atopic dermatitis at baseline A baseline itch numeric rating scale score of 4 or greater; and have one or more characteristics selected from the group consisting of an Investigator's Global Assessment score of at least 3 at baseline.

[0200] The disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis; wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater; Having ≥10% of the body surface area involved in atopic dermatitis at baseline A baseline itch numeric rating scale score of 4 or greater; and have one or more characteristics selected from the group consisting of an Investigator's Global Assessment score of at least 3 at baseline.

[0201] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) ruxolitinib phosphate on a free base basis; wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater; Having ≥10% of the body surface area involved in atopic dermatitis at baseline A baseline itch numeric rating scale score of 4 or greater; and have one or more characteristics selected from the group consisting of an Investigator's Global Assessment score of at least 3 at baseline.

[0202] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis; wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater; Having ≥10% of the body surface area involved in atopic dermatitis at baseline A baseline itch numeric rating scale score of 4 or greater; and have one or more characteristics selected from the group consisting of an Investigator's Global Assessment score of at least 3 at baseline.

[0203] In some embodiments, the patient is A baseline Eczema Area and Severity Index score of 16 or greater; Having ≥10% of the body surface area involved in atopic dermatitis at baseline A baseline itch numeric rating scale score of 4 or higher; Investigator's Global Assessment score ≥ 3 at baseline; Be between 12 and 85 years old, and having one or more characteristics selected from the group consisting of a history of atopic dermatitis for at least two years.

[0204] In some embodiments, the patient is A baseline Eczema Area and Severity Index score of 16 or greater; ≥10% of body surface area involved in atopic dermatitis at baseline; and have one or more characteristics selected from the group consisting of: Investigator's Global Assessment score of 3 at baseline.

[0205] In some embodiments, the patient has a baseline Eczema Area and Severity Index score of 16 or greater.

[0206] In some embodiments, the patient has 10% or more of their body surface area involved in atopic dermatitis at baseline.

[0207] In some embodiments, the patient has 10%-20% of their body surface area involved in atopic dermatitis at baseline.

[0208] In some embodiments, the patient has an Itch Numeric Rating Scale score of 4 or greater at baseline.

[0209] In some embodiments, the patient has an Investigator's Global Assessment score of 3 at baseline.

[0210] In some embodiments, the patient suffers from moderate atopic dermatitis.

[0211] In some embodiments, the patient suffers from moderate to severe atopic dermatitis.

[0212] In some embodiments, the patient has a baseline Eczema Area and Severity Index of 16 or greater and a baseline body surface area involved in atopic dermatitis of 10% or greater. In some embodiments of this paragraph, the body surface area involved in atopic dermatitis is alternatively between 10% and 20% at baseline.

[0213] In some embodiments, the patient has a baseline Eczema Area and Severity Index of 16 or greater, a baseline body surface area involved in atopic dermatitis of 10% or greater, and a baseline Itch Numeric Rating Scale score of 4 or greater. In some embodiments of this paragraph, the body surface area involved in atopic dermatitis is alternatively between 10% and 20% at baseline.

[0214] In some embodiments, patients with a baseline Eczema Area and Severity Index score of 16 or greater and 10% or greater of their body surface area involved in atopic dermatitis at baseline achieve a 75% improvement in their Eczema Area and Severity Index score from baseline at week 2 of said administration. In some embodiments of this paragraph, the body surface area involved in atopic dermatitis is alternatively between 10% and 20% at baseline.

[0215] In some embodiments, patients with a baseline Eczema Area and Severity Index score of 16 or greater and 10% or greater of their body surface area involved in atopic dermatitis at baseline achieve a 75% improvement in their Eczema Area and Severity Index score from baseline at week 4 of said administration. In some embodiments of this paragraph, the body surface area involved in atopic dermatitis is alternatively between 10% and 20% at baseline.

[0216] In some embodiments, patients with a baseline Eczema Area and Severity Index score of 16 or greater and 10% or greater of their body surface area involved in atopic dermatitis at baseline achieve a 75% improvement in their Eczema Area and Severity Index score from baseline at week 8 of said administration. In some embodiments of this paragraph, the body surface area involved in atopic dermatitis is alternatively between 10% and 20% at baseline.

[0217] In some embodiments, patients with an Eczema Area and Severity Index score of 16 or greater at baseline and 10% or more of their body surface area involved in atopic dermatitis at baseline achieve an Investigator's Global Assessment score of 0 or 1 with at least a 2 point improvement from baseline at 2 weeks of said administration. In some embodiments of this paragraph, the body surface area involved in atopic dermatitis is alternatively between 10% and 20% at baseline.

[0218] In some embodiments, patients with an Eczema Area and Severity Index score of 16 or greater at baseline and 10% or more of their body surface area involved in atopic dermatitis at baseline achieve an Investigator's Global Assessment score of 0 or 1 with at least a 2 point improvement from baseline at 4 weeks of said administration. In some embodiments of this paragraph, the body surface area involved in atopic dermatitis is alternatively between 10% and 20% at baseline.

[0219] In some embodiments, patients with an Eczema Area and Severity Index score of 16 or greater at baseline and 10% or more of their body surface area involved in atopic dermatitis at baseline achieve an Investigator's Global Assessment score of 0 or 1 with at least a 2 point improvement from baseline at 8 weeks of said administration. In some embodiments of this paragraph, the body surface area involved in atopic dermatitis is alternatively between 10% and 20% at baseline.

[0220] In some embodiments, the patient has an Eczema Area and Severity Index of 16 or greater at baseline, 10% or greater body surface area involved in atopic dermatitis at baseline, and achieves at least a 4 point reduction in Itch Numeric Rating Scale score from baseline at week 2 of said administration. In some embodiments of this paragraph, the body surface area involved in atopic dermatitis is alternatively between 10% and 20% at baseline.

[0221] In some embodiments, the patient has an Eczema Area and Severity Index of 16 or greater at baseline, 10% or greater body surface area involved in atopic dermatitis at baseline, and achieves at least a 4 point reduction in Itch Numeric Rating Scale score from baseline at week 4 of said administration. In some embodiments of this paragraph, the body surface area involved in atopic dermatitis is alternatively between 10% and 20% at baseline.

[0222] In some embodiments, patients with a baseline Eczema Area and Severity Index of 16 or greater and 10% or greater body surface area involved in atopic dermatitis at baseline achieve at least a 4 point reduction in Itch Numeric Rating Scale score from baseline at week 8 of said administration. In some embodiments of this paragraph, the body surface area involved in atopic dermatitis is alternatively between 10% and 20% at baseline.

[0223] In some embodiments, patients with a baseline Eczema Area and Severity Index of 16 or greater, a baseline body surface area involved in atopic dermatitis of 10% or greater, and a baseline Itch Numeric Rating Scale score of 4 or greater achieve at least a 4 point reduction in Itch Numeric Rating Scale score from baseline at week 2 of said administration. In some embodiments of this paragraph, the body surface area involved in atopic dermatitis is alternatively between 10% and 20% at baseline.

[0224] In some embodiments, patients with a baseline Eczema Area and Severity Index of 16 or greater, a baseline body surface area involved in atopic dermatitis of 10% or greater, and a baseline Itch Numeric Rating Scale score of 4 or greater achieve at least a 4 point reduction in Itch Numeric Rating Scale score from baseline at week 4 of said administration. In some embodiments of this paragraph, the body surface area involved in atopic dermatitis is alternatively between 10% and 20% at baseline.

[0225] In some embodiments, patients with a baseline Eczema Area and Severity Index of 16 or greater, a baseline body surface area involved in atopic dermatitis of 10% or greater, and a baseline Itch Numeric Rating Scale score of 4 or greater achieve at least a 4 point reduction in Itch Numeric Rating Scale score from baseline at week 8 of said administration. In some embodiments of this paragraph, the body surface area involved in atopic dermatitis is alternatively between 10% and 20% at baseline.

[0226] In some embodiments, the patient has a baseline Eczema Area and Severity Index of 16 or greater, a baseline body surface area involved in atopic dermatitis of 10% or greater, and an Investigator's Global Assessment score at the Screening and Baseline visits of 3 or greater. In some embodiments of this paragraph, the body surface area involved in atopic dermatitis is alternatively between 10% and 20% at baseline.

[0227] In some embodiments, the patient has a baseline Eczema Area and Severity Index of 16 or greater, a baseline body surface area involved in atopic dermatitis of 10% or greater, and an Investigator's Global Assessment score of 3 at the Screening and Baseline visits. In some embodiments of this paragraph, the body surface area involved in atopic dermatitis is alternatively between 10% and 20% at baseline.

[0228] In some embodiments, the patient has characteristics including an Eczema Area and Severity Index score of 16 or greater at baseline, 10% or greater body surface area involved in atopic dermatitis at baseline, being between 12 and 85 years old, and having at least a 2-year history of atopic dermatitis. In some embodiments, the characteristics further include an Investigator's Global Assessment score of 3 or greater at Screening and Baseline visits. In some embodiments, the characteristics further include an Investigator's Global Assessment score of 3 at Screening and Baseline visits. In some embodiments, the characteristics further include an Itch Numeric Rating Scale score of 4 or greater at baseline. In some embodiments of the embodiments of this paragraph, the body surface area involved in atopic dermatitis is alternatively between 10% and 20% at baseline.

[0229] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; the patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of said administration; The patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of dosing; and wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater; Having ≥10% of the body surface area involved in atopic dermatitis at baseline A baseline itch numeric rating scale score of 4 or higher; Investigator's Global Assessment score of at least 3 at baseline; be 12 years of age or older; and having one or more characteristics selected from the group consisting of a history of atopic dermatitis for at least two years.

[0230] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; the patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of said administration; The patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of dosing; and wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater; Having ≥10% of the body surface area involved in atopic dermatitis at baseline be 12 years of age or older; and having one or more characteristics selected from the group consisting of a history of atopic dermatitis for at least two years.

[0231] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; the patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of said administration; The patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of dosing; and wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater; Having ≥10% of the body surface area involved in atopic dermatitis at baseline A baseline itch numeric rating scale score of 4 or higher; be 12 years of age or older; and having one or more characteristics selected from the group consisting of a history of atopic dermatitis for at least two years.

[0232] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; the patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of said administration; The patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of dosing; and wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater; Having ≥10% of the body surface area involved in atopic dermatitis at baseline A baseline itch numeric rating scale score of 4 or higher; Investigator's Global Assessment score of at least 3 at baseline; be 12 years of age or older; and having one or more characteristics selected from the group consisting of a history of atopic dermatitis for at least two years.

[0233] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 0.75% (w / w) ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; the patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of said administration; The patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of dosing; and wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater; Having ≥10% of the body surface area involved in atopic dermatitis at baseline A baseline itch numeric rating scale score of 4 or higher; Investigator's Global Assessment score of 3 at screening and baseline; be 12 years of age or older; and having one or more characteristics selected from the group consisting of a history of atopic dermatitis for at least two years.

[0234] In another embodiment, the present disclosure provides a method of treating atopic dermatitis in a human patient having atopic dermatitis, the method comprising: (1) 0.75% (w / w) ruxolitinib phosphate on a free base basis, (2) administering to the skin of the human patient in need thereof twice daily a composition comprising: (a) a means for effecting dose-dependent skin penetration of the ruxolitinib phosphate; and (b) a means for effecting dose-dependent skin penetration of the ruxolitinib phosphate, wherein the patient achieves successful IGA treatment.

[0235] In another embodiment, the present disclosure provides a method of treating atopic dermatitis in a human patient having atopic dermatitis, the method comprising: (1) 0.75% (w / w) ruxolitinib phosphate on a free base basis, (2) administering to the skin of the human patient in need thereof twice daily a composition comprising: (a) a means for effecting dose-dependent skin penetration of the ruxolitinib phosphate; and (b) a means for effecting dose-dependent skin penetration of the ruxolitinib phosphate, wherein the patient achieves EASI-75.

[0236] In another embodiment, the present disclosure provides a method of treating atopic dermatitis in a human patient having atopic dermatitis, the method comprising: (1) 0.75% (w / w) ruxolitinib phosphate on a free base basis, (2) a means for effecting dose-dependent skin penetration of the ruxolitinib phosphate, said composition comprising said ruxolitinib phosphate and said ...

[0237] In another embodiment, the present disclosure provides a method of treating atopic dermatitis in a human patient having atopic dermatitis, the method comprising: (1) 0.75% (w / w) ruxolitinib phosphate on a free base basis, (2) a means for effecting dose-dependent skin penetration of the ruxolitinib phosphate, said composition comprising said ruxolitinib phosphate and said ...

[0238] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; the patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of said administration; The patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of dosing; and wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater; Having ≥10% of the body surface area involved in atopic dermatitis at baseline A baseline itch numeric rating scale score of 4 or higher; Investigator's Global Assessment score ≥ 3 at screening and baseline; be 12 years of age or older; and having one or more characteristics selected from the group consisting of a history of atopic dermatitis for at least two years.

[0239] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; the patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of said administration; The patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of dosing; and wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater; Having ≥10% of the body surface area involved in atopic dermatitis at baseline be 12 years of age or older; and having one or more characteristics selected from the group consisting of a history of atopic dermatitis for at least two years.

[0240] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; the patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of said administration; The patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of dosing; and wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater; Having ≥10% of the body surface area involved in atopic dermatitis at baseline A baseline itch numeric rating scale score of 4 or higher; be 12 years of age or older; and having one or more characteristics selected from the group consisting of a history of atopic dermatitis for at least two years.

[0241] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; the patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of said administration; The patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of dosing; and wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater; Having ≥10% of the body surface area involved in atopic dermatitis at baseline A baseline itch numeric rating scale score of 4 or higher; Investigator's Global Assessment score of at least 3 at screening and baseline; be 12 years of age or older; and having one or more characteristics selected from the group consisting of a history of atopic dermatitis for at least two years.

[0242] The present disclosure also provides a method of treating atopic dermatitis in a human patient, the method comprising administering twice daily to the skin of a human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis; wherein the administration is maintained for at least 8 weeks; the patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of said administration; The patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of dosing; and wherein the patient is A baseline Eczema Area and Severity Index score of 16 or greater; Having ≥10% of the body surface area involved in atopic dermatitis at baseline A baseline itch numeric rating scale score of 4 or higher; Investigator's Global Assessment score of 3 at screening and baseline; be 12 years of age or older; and having one or more characteristics selected from the group consisting of a history of atopic dermatitis for at least two years.

[0243] In another embodiment, the present disclosure provides a method of treating atopic dermatitis in a human patient having atopic dermatitis, the method comprising: (1) 1.5% (w / w) ruxolitinib phosphate on a free base basis, (2) administering to the skin of the human patient in need thereof twice daily a composition comprising: (a) a means for effecting dose-dependent skin penetration of the ruxolitinib phosphate; and (b) a means for effecting dose-dependent skin penetration of the ruxolitinib phosphate, wherein the patient achieves successful IGA treatment.

[0244] In another embodiment, the present disclosure provides a method of treating atopic dermatitis in a human patient having atopic dermatitis, the method comprising: (1) 1.5% (w / w) ruxolitinib phosphate on a free base basis, (2) administering to the skin of the human patient in need thereof twice daily a composition comprising: (a) a means for effecting dose-dependent skin penetration of the ruxolitinib phosphate; and (b) a means for effecting dose-dependent skin penetration of the ruxolitinib phosphate, wherein the patient achieves EASI-75.

[0245] In another embodiment, the present disclosure provides a method of treating atopic dermatitis in a human patient having atopic dermatitis, the method comprising: (1) 1.5% (w / w) ruxolitinib phosphate on a free base basis, (2) a means for effecting dose-dependent skin penetration of the ruxolitinib phosphate, said composition comprising said ruxolitinib phosphate and said ...

[0246] In another embodiment, the present disclosure provides a method of treating atopic dermatitis in a human patient having atopic dermatitis, the method comprising: (1) 1.5% (w / w) ruxolitinib phosphate on a free base basis, (2) a means for effecting dose-dependent skin penetration of the ruxolitinib phosphate, said composition comprising said ruxolitinib phosphate and said ...

[0247] definition As used herein, "ruxolitinib phosphate" means the phosphate salt of ruxolitinib, where ruxolitinib and phosphate are in a 1:1 ratio.

[0248] In some embodiments, "cream" refers to a semi-solid formulation of an emulsion for application to the skin.

[0249] When the method refers to "day 2", "week 4", "week 8", "week 12", "within 36 hours", or "within 12 hours" of administration, this refers to the period after the first administration of the cream formulation, when administration is not interrupted. For example, when the method refers to the reduction in itch NRS score from baseline at week 8 in patients administered the cream formulation BID, this means that the itch NRS score was assessed 8 weeks after BID administration of the cream formulation, without skipping a day after the first administration of the cream formulation. With respect to the itch NRS, since ruxolitinib cream or vehicle is applied in the morning and the itch NRS is measured in the evening (see Phase 2 and Phase 3 studies in the Examples), "day 1" means about 12 hours after administration, "day 2" means about 36 hours after administration, "day 3" means about 2.5 days after administration, etc.

[0250] As used herein, "rapid reduction in itch" means a statistically significant reduction in the Itch NRS score within 12 hours of the first administration of ruxolitinib cream (or "day 1" as used herein) compared to vehicle.

[0251] The "Hanifin and Rajka Criteria" are described in Hanifin JM, Rajka G. "Diagnostic features of atopic dermatitis," Acta Derm Venereol Suppl (Stockh) 1980; 92:44-47, which is incorporated herein by reference in its entirety.

[0252] As used herein, "%BSA" refers to the percentage of total body surface area affected by AD, which can be determined to the nearest 0.1% ("finger palm print") for areas identified as being treated with ruxolitinib cream at baseline (excluding face and interstitial areas, or alternatively excluding scalp), with, as a guide, 1% for the fingers and palm and 0.1% for the thumb.

[0253] As used herein, "itch NRS score" refers to the itch numerical rating scale. The itch NRS is a daily patient-reported measure of itch intensity (24-hour recall). Subjects are asked to assess the severity of their itch due to AD by selecting a number from 0 (no itch) to 10 (worst itch imaginable) that best represents the worst level of itch in the past 24 hours. In a non-limiting example, patients can be issued a handheld device (eDiary) to record the severity of itch. Patients can be instructed to complete the eDiary every night.

[0254] As used herein, "EASI" refers to the Eczema Area and Severity Index. The EASI scoring system is a disease measurement that has been validated in clinical studies (Hanifin JM, et al, Exp Dermatol 2001;10:11-18). The EASI severity hierarchy is as follows: 0=clear, 0.1-1.0=almost clear, 1.1-7.0=mild, 7.1-21.0=moderate, 21.1-50.0=severe, 50.1-72.0=very severe.

[0255] As used herein, "EASI-75" refers to a 75% or greater improvement in a patient's Eczema Area and Severity Index.

[0256] As used herein, "BID" refers to twice a day.

[0257] As used herein, "QD" refers to once daily.

[0258] As used herein, "statistically significant" means a p-value of less than 0.05 (preferably less than 0.001, and most preferably less than 0.0001).

[0259] As used herein, "IGA" refers to Investigator Global Assessment. The IGA grades are shown in the table below. [Table 1]

[0260] As used herein, "IGA-TS" means Investigator's Global Assessment of Treatment Success, which is an IGA score of 0 or 1 with an improvement of ≥2 grades from baseline.

[0261] As used herein, the phrase "pharmacologically acceptable" means compounds, materials, compositions, and / or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and animals. In some embodiments, "pharmacologically acceptable" means approved by a federal or state regulatory agency for use in animals, more specifically humans, or listed in the United States Pharmacopeia or other generally recognized pharmacopoeias.

[0262] The present invention also includes pharma- ceutically acceptable salts of the compounds described herein. As used herein, a "pharma- ceutically acceptable salt" is a derivative of the disclosed compound, where the parent compound is modified by converting an existing acid or base moiety into its salt form. Examples of pharma- ceutically acceptable salts include, but are not limited to, inorganic or organic acid salts of basic residues such as amines, alkali or organic salts of acidic residues such as carboxylic acids, and the like. The pharma- ceutically acceptable salts of the present invention include conventional non-toxic salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. The pharma- ceutically acceptable salts of the present invention can be synthesized from the parent compound containing a basic or acidic moiety by conventional chemical methods. In general, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or an organic solvent, or in a mixture of the two, generally in non-aqueous media such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile (MeCN) being preferred. Lists of suitable salts can be found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418, and Journal of Pharmaceutical Science, 66, 2 (1977), each of which is incorporated herein by reference in its entirety. In some embodiments, the pharma- ceutically acceptable salt is a phosphate, sulfate, or maleate salt.

[0263] As used herein, "PROMIS" refers to the Patient-Reported Outcomes Measurement Information System (PROMIS®), a widely used and accepted set of patient-reported outcome measures developed and psychometrically supported with robust clinical outcome assessment development methods. The selected PROMIS Short Form-Sleep Related Disorders (8a) and Short Form-Sleep Disorders (8b) questionnaires were adapted to be completed in a daily diary with 24-hour recall. The Short Form-Sleep Related Disorders (8a) is collected in the evening and the Short Form-Sleep Disorders (8b) is collected in the morning during a vehicle-controlled period.

[0264] As used herein, "minimal clinically important difference" or "MCID" refers to a 2-3 point reduction in the Itch NRS compared to baseline.

[0265] As used herein, "clinically relevant improvement" or "CRI" refers to a reduction in the Itch NRS of 4 or more points compared to baseline.

[0266] As used herein, the term "emulsifier component" refers, in one aspect, to a substance or mixture of substances that maintain elements or particles in suspension within a fluid medium. In some embodiments, the emulsifier component allows the oil phase to form an emulsion when combined with water. In some embodiments, the emulsifier component refers to one or more non-ionic surfactants.

[0267] As used herein, the term "occlusive agent component" refers to a hydrophobic agent or mixture of hydrophobic agents that forms an occlusive film on the skin that reduces transepidermal water loss (TEWL) by preventing evaporation of water from the stratum corneum.

[0268] As used herein, the term "sclerosing agent component" refers to a substance or mixture of substances that increases the viscosity and / or consistency of a cream or improves the rheology of the cream.

[0269] As used herein, the term "emollient ingredient" refers to an agent that softens or soothes the skin or soothes irritated internal surfaces.

[0270] As used herein, the term "stabilizer component" refers to a substance or mixture of substances that improves the stability of a cream and / or the compatibility of ingredients in the crumb. In some embodiments, the stabilizer component prevents emulsion coalescence and stabilizes droplets in oil-in-water emulsions.

[0271] As used herein, the term "solvent component" refers to a liquid substance or mixture of liquid substances that can dissolve ruxolitinib (or a salt thereof) or other substances in the cream. In some embodiments, the solvent component is a liquid substance or mixture of liquid substances in which ruxolitinib or a pharma- ceutically acceptable salt thereof has reasonable solubility. For example, the solubility of ruxolitinib (free base) or its phosphate salt (1:1 salt) is reported in Table 1. In some embodiments, the solvent is a substance or mixture of substances in which ruxolitinib or a pharma- ceutically acceptable salt thereof (whichever is used) has a solubility of at least about 10 mg / mL or more, at least about 15 mg / mL or more, or at least about 20 mg / mL or more, as measured as described in Example 2.

[0272] As used herein, the phrase "antimicrobial preservative component" is a substance or mixture of substances that inhibits the growth of microorganisms in the cream.

[0273] As used herein, the phrase "chelator component" refers to a compound or mixture of compounds that has the ability to strongly bind metal ions.

[0274] As used herein, "wt % of the emulsion" means the percent concentration of a component in the emulsion on a weight / weight basis. For example, 1% w / w of component A = [(mass of component A) / (total mass of emulsion)] x 100.

[0275] As used herein, "weight percent of emulsion based on free base" of ruxolitinib or its pharma- ceutically acceptable salt means that %w / w is calculated based on the weight of ruxolitinib in the entire emulsion.For example, "1.5%w / w based on free base" of ruxolitinib phosphate means that for 100 grams of total formulation, there is 1.98 grams of ruxolitinib phosphate in the emulsion (which corresponds to 1.5 grams of free base, ruxolitinib).

[0276] As used herein, the term "ingredient" can mean a substance or a mixture of substances.

[0277] As used herein, the term "fatty acid" refers to a saturated or unsaturated fatty acid. In some embodiments, the fatty acid is in a mixture of different fatty acids. In some embodiments, the fatty acid has an average of about 8 to about 30 carbons. In some embodiments, the fatty acid has an average of about 12 to 20, 14 to 20, or 16 to 18 carbons. Suitable fatty acids include, but are not limited to, cetylic acid, stearic acid, lauric acid, myristic acid, erucic acid, palmitic acid, palmitic acid, capric acid, caprylic acid, oleic acid, linoleic acid, linolenic acid, hydroxystearic acid, 12-hydroxystearic acid, cetostearic acid, isostearic acid, sesquioleic acid, sesqui-9-octadecanoic acid, sesquiisooctadecanoic acid, behenic acid, isobehenic acid, and arachidonic acid, or mixtures thereof.

[0278] As used herein, the term "fatty alcohol" refers to a saturated or unsaturated aliphatic alcohol. In some embodiments, the fatty alcohol is in a mixture of different fatty alcohols. In some embodiments, the fatty alcohol has an average of about 12 to about 20, about 14 to about 20, or about 16 to about 18 carbons. Suitable fatty alcohols include, but are not limited to, stearyl alcohol, lauryl alcohol, palmityl alcohol, cetyl alcohol, capryl alcohol, caprylyl alcohol, oleyl alcohol, linolenyl alcohol, arachidonic alcohol, behenyl alcohol, isobehenyl alcohol, selachyl alcohol, chimyl alcohol, and linoleyl alcohol, or mixtures thereof.

[0279] As used herein, the term "polyalkylene glycol", used alone or in combination with other terms, refers to a polymer comprising oxyalkylene monomer units or a copolymer of different oxyalkylene monomer units, where the alkylene groups have 2 to 6, 2 to 4, or 2 to 3 carbon atoms. As used herein, the term "oxyalkylene", used alone or in combination with other terms, refers to a group of formula -O-alkylene-. In some embodiments, the polyalkylene glycol is a polyethylene glycol.

[0280] As used herein, the term "sorbitan fatty ester" includes products derived from sorbitan or sorbitol and fatty acids, and optionally poly(ethylene glycol) units, including sorbitan esters and polyethoxylated sorbitan esters. In some embodiments, the sorbitan fatty esters are polyethoxylated sorbitan esters.

[0281] As used herein, the term "sorbitan ester" refers to a compound or mixture of compounds derived from the esterification of sorbitol and at least one fatty acid. Fatty acids useful for deriving sorbitan esters include, but are not limited to, those described herein. Suitable sorbitan esters include, but are not limited to, the Span™ series (available from Uniqema). The Span™ series includes Span 20 (sorbitan monolaurate), 40 (sorbitan monopalmitate), 60 (sorbitan monostearate), 65 (sorbitan tristearate), 80 (sorbitan monooleate), and 85 (sorbitan trioleate). Other suitable sorbitan esters include those described in RC Rowe and PJ Shesky, Handbook of pharmaceutical excipients, (2006), 5th ed., which is incorporated herein by reference in its entirety.

[0282] As used herein, the term "polyethoxylated sorbitan ester" refers to a compound or mixture of compounds derived from the ethoxylation of a sorbitan ester. The polyoxyethylene portion of the compound may be between the fatty ester and the sorbitan portion. As used herein, the term "sorbitan ester" refers to a compound or mixture of compounds derived from the esterification of sorbitol and at least one fatty acid. Fatty acids useful for deriving polyethoxylated sorbitan esters include, but are not limited to, those described herein. In some embodiments, the polyoxyethylene portion of the compound or mixture has about 2 to about 200 oxyethylene units. In some embodiments, the polyoxyethylene portion of the compound or mixture has about 2 to about 100 oxyethylene units. In some embodiments, the polyoxyethylene portion of the compound or mixture has about 4 to about 80 oxyethylene units. In some embodiments, the polyoxyethylene portion of the compound or mixture has about 4 to about 40 oxyethylene units. In some embodiments, the polyoxyethylene portion of the compound or mixture has about 4 to about 20 oxyethylene units. Suitable polyethoxylated sorbitan esters include, but are not limited to, the Tween™ series (available from Uniqema), including Tween 20 (POE(20) sorbitan monolaurate), 21 (POE(4) sorbitan monolaurate), 40 (POE(20)) sorbitan monopalmitate), 60 (POE(20) sorbitan monostearate), 60K (POE(20) sorbitan monostearate), 61 (POE(4) sorbitan monostearate), 65 (POE(20) sorbitan tristearate), 80 (POE(20) sorbitan monooleate), 80K (POE(20) sorbitan monooleate), 81 (POE(5) sorbitan monooleate), and 85 (POE(20) sorbitan trioleate). As used herein, the abbreviation "POE" refers to polyoxyethylene. The number following the POE abbreviation refers to the number of oxyethylene repeat units in the compound.Other suitable polyethoxylated sorbitan esters include the polyoxyethylene sorbitan fatty acid esters described in RC Rowe and PJ Shesky, Handbook of pharmaceutical excipients, (2006), 5th ed., which is incorporated herein by reference in its entirety. In some embodiments, the polyethoxylated sorbitan ester is a polysorbate. In some embodiments, the polyethoxylated sorbitan ester is polysorbate 20.

[0283] As used herein, the term "glyceryl fatty acid ester" refers to a mono-, di-, or triglyceride of a fatty acid. The glyceryl fatty acid ester may be optionally substituted with a sulfonic acid group, or a pharma- ceutically acceptable salt thereof. Suitable fatty acids for deriving the glyceride of a fatty acid include, but are not limited to, those described herein. In some embodiments, the glyceryl fatty acid ester is a monoglyceride of a fatty acid having 12 to 18 carbon atoms. In some embodiments, the glyceryl fatty acid ester is glyceryl stearate.

[0284] As used herein, the term "triglyceride" refers to a triglyceride of a fatty acid. In some embodiments, the triglyceride is a medium chain triglyceride.

[0285] As used herein, the term "alkylene glycol" refers to a group of formula -O-alkylene-, where the alkylene group has from 2 to 6, 2 to 4, or 2 to 3 carbon atoms. In some embodiments, the alkylene glycol is propylene glycol (1,2-propanediol).

[0286] As used herein, the term "polyethylene glycol" refers to a compound of the formula -O-CH 2 -CH 2- refers to a polymer containing ethylene glycol monomer units. Suitable polyethylene glycols may have a free hydroxyl group at each end of the polymer molecule or one or more hydroxyl groups etherified with a lower alkyl, such as a methyl group. Even more suitable are derivatives of polyethylene glycol with esterifiable carboxy groups. The polyethylene glycols useful in the present disclosure may be polymers of any chain length or molecular weight, as well as may contain branching. In some embodiments, the average molecular weight of the polyethylene glycol is about 200 to about 9000. In some embodiments, the average molecular weight of the polyethylene glycol is about 200 to about 5000. In some embodiments, the average molecular weight of the polyethylene glycol is about 200 to about 900. In some embodiments, the average molecular weight of the polyethylene glycol is about 400. Suitable polyethylene glycols include, but are not limited to, polyethylene glycol-200, polyethylene glycol-300, polyethylene glycol-400, polyethylene glycol-600, and polyethylene glycol-900. The number following the dash in the name refers to the average molecular weight of the polymer.

[0287] In some embodiments, "about" means ±10% of the value.

[0288] Cream formulation In some embodiments, the cream formulation is an oil-in-water emulsion. In some embodiments, the cream is a solubilized cream. In some embodiments, the cream has a pH of about 2.8 to about 3.6. In the context of pH, "about" refers to ±0.3 (preferably ±0.2 or more preferably ±0.1).

[0289] In some embodiments, the cream comprises an oil-in-water emulsion containing 1.5% (w / w) ruxolitinib phosphate on a free base basis.

[0290] In some embodiments, the cream is an oil-in-water emulsion as described in U.S. Patent Application Publication No. 2015 / 0250790, which is incorporated by reference in its entirety, in particular Examples 3-6 of U.S. Patent Application Publication No. 2015 / 0250790 (particularly Tables 3-5 and the accompanying text), which are incorporated by reference herein.

[0291] In some embodiments, the oil component is present in an amount of about 10% to about 40% by weight of the emulsion.

[0292] In some embodiments, the oil component is present in an amount from about 10% to about 24% by weight of the emulsion.

[0293] In some embodiments, the oil component is present in an amount from about 15% to about 24% by weight of the emulsion.

[0294] In some embodiments, the oil component is present in an amount from about 18% to about 24% by weight of the emulsion.

[0295] In some embodiments, the oil component comprises one or more materials independently selected from petrolatum, fatty alcohols, mineral oils, triglycerides, and silicone oils.

[0296] In some embodiments, the oil component comprises one or more materials independently selected from white petrolatum, cetyl alcohol, stearyl alcohol, light mineral oil, medium chain triglycerides, and dimethicone.

[0297] In some embodiments, the oil component comprises an occlusive agent component.

[0298] In some embodiments, the occlusive agent component is present in an amount of about 2% to about 15% by weight of the emulsion.

[0299] In some embodiments, the occlusive agent component is present in an amount of about 5% to about 10% by weight of the emulsion.

[0300] In some embodiments, the occlusive agent component comprises one or more materials selected from fatty acids (e.g., lanolin acid), fatty alcohols (e.g., lanolin alcohol), hydrocarbon oils and waxes (e.g., petrolatum), polyhydric alcohols (e.g., propylene glycol), silicones (e.g., dimethicone), sterols (e.g., cholesterol), vegetable or animal fats (e.g., cocoa butter), vegetable waxes (e.g., carnauba wax), and wax esters (e.g., beeswax).

[0301] In some embodiments, the occlusive agent component comprises one or more materials selected from lanolin acid fatty alcohol, lanolin alcohol, petrolatum, propylene glycol, dimethicone, cholesterol, cocoa butter, carnauba wax, and beeswax.

[0302] In some embodiments, the occlusive agent component comprises petrolatum.

[0303] In some embodiments, the occlusive agent component comprises white petrolatum.

[0304] In some embodiments, the oil component comprises a stiffening agent component.

[0305] In some embodiments, the hardener component is present in an amount of about 2% to about 8% by weight of the emulsion.

[0306] In some embodiments, the hardener component is present in an amount of about 3% to about 6% by weight of the emulsion.

[0307] In some embodiments, the hardener component is present in an amount of about 4% to about 7% by weight of the emulsion.

[0308] In some embodiments, the stiffening agent component comprises one or more materials independently selected from fatty alcohols.

[0309] In some embodiments, the curing agent component is12-20 The composition includes one or more materials independently selected from fatty alcohols.

[0310] In some embodiments, the curing agent component is 16-18 The composition includes one or more materials independently selected from fatty alcohols.

[0311] In some embodiments, the stiffening agent component comprises one or more materials independently selected from cetyl alcohol and stearyl alcohol.

[0312] In some embodiments, the oil component comprises an emollient component.

[0313] In some embodiments, the emollient component is present in an amount from about 5% to about 15% by weight of the emulsion.

[0314] In some embodiments, the emollient component is present in an amount from about 7% to about 13% by weight of the emulsion.

[0315] In some embodiments, the emollient component comprises one or more materials independently selected from mineral oil and triglycerides.

[0316] In some embodiments, the emollient component comprises one or more materials independently selected from light mineral oil and medium chain triglycerides.

[0317] In some embodiments, the emollient component comprises one or more materials independently selected from light mineral oil, medium chain triglycerides, and dimethicone.

[0318] In some embodiments, water is present in an amount from about 35% to about 65% by weight of the emulsion.

[0319] In some embodiments, water is present in an amount of about 40% to about 60% by weight of the emulsion.

[0320] In some embodiments, water is present in an amount from about 45% to about 55% by weight of the emulsion.

[0321] In some embodiments, the emulsifier component is present in an amount from about 1% to about 9% by weight of the emulsion.

[0322] In some embodiments, the emulsifier component is present in an amount from about 2% to about 6% by weight of the emulsion.

[0323] In some embodiments, the emulsifier component is present in an amount of about 3% to about 5% by weight of the emulsion.

[0324] In some embodiments, the emulsifier component is present in an amount from about 4% to about 7% by weight of the emulsion.

[0325] In some embodiments, the emulsion comprises an emulsifier component and a hardener component, wherein the combined amount of the emulsifier component and the hardener component is at least about 8% by weight of the emulsion.

[0326] In some embodiments, the emulsifier component comprises one or more materials independently selected from glyceryl fatty acid esters and sorbitan fatty acid esters.

[0327] In some embodiments, the emulsifier component comprises one or more materials independently selected from glyceryl stearate and polysorbate 20.

[0328] In some embodiments, the emulsion further comprises a stabilizer component.

[0329] In some embodiments, the stabilizer component is present in an amount of about 0.05% to about 5% by weight of the emulsion.

[0330] In some embodiments, the stabilizer component is present in an amount of about 0.1% to about 2% by weight of the emulsion.

[0331] In some embodiments, the stabilizer component is present in an amount of about 0.3% to about 0.5% by weight of the emulsion.

[0332] In some embodiments, the stabilizer component comprises one or more materials independently selected from polysaccharides.

[0333] In some embodiments, the stabilizer component comprises xanthan gum.

[0334] In some embodiments, the emulsion further comprises a solvent component.

[0335] In some embodiments, the solvent component is present in an amount of about 10% to about 35% by weight of the emulsion.

[0336] In some embodiments, the solvent component is present in an amount of about 15% to about 30% by weight of the emulsion.

[0337] In some embodiments, the solvent component is present in an amount of about 20% to about 25% by weight of the emulsion.

[0338] In some embodiments, the solvent component comprises one or more materials independently selected from alkylene glycols and polyalkylene glycols.

[0339] In some embodiments, the solvent component comprises one or more materials independently selected from propylene glycol and polyethylene glycol.

[0340] In some embodiments, the emulsion comprises: about 35% to about 65% water by weight of the emulsion; an oil component of about 10% to about 40% by weight of the emulsion; from about 1% to about 9% by weight of the emulsion of an emulsifier component; a solvent component of about 10% to about 35% by weight of the emulsion; From about 0.05% to about 5% by weight of the emulsion of a stabilizer component; and The emulsion contains 0.5% to 1.5% by weight of ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0341] In some embodiments, the emulsion comprises: about 35% to about 65% water by weight of the emulsion; an oil component of about 10% to about 24% by weight of the emulsion; from about 1% to about 9% by weight of the emulsion of an emulsifier component; a solvent component of about 10% to about 35% by weight of the emulsion; From about 0.05% to about 5% by weight of the emulsion of a stabilizer component; and The emulsion contains 0.5% to 1.5% by weight of ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0342] In some embodiments, the emulsion comprises: about 40% to about 60% water by weight of the emulsion; an oil component of about 15% to about 30% by weight of the emulsion; an emulsifier component, from about 2% to about 6% by weight of the emulsion; a solvent component of about 15% to about 30% by weight of the emulsion; From about 0.1% to about 2% by weight of the emulsion of a stabilizer component; and The emulsion contains 0.5% to 1.5% by weight of ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0343] In some embodiments, the emulsion comprises: about 40% to about 60% water by weight of the emulsion; an oil component of about 15% to about 30% by weight of the emulsion; an emulsifier component, from about 2% to about 6% by weight of the emulsion; a solvent component of about 15% to about 24% by weight of the emulsion; From about 0.1% to about 2% by weight of the emulsion of a stabilizer component; and The emulsion contains 0.5% to 1.5% by weight of ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0344] In some embodiments, the emulsion comprises: about 45% to about 55% water by weight of the emulsion; an oil component of about 15% to about 24% by weight of the emulsion; an emulsifier component, from about 3% to about 5% by weight of the emulsion; a solvent component of about 20% to about 25% by weight of the emulsion; about 0.3% to about 0.5% by weight of the emulsion of a stabilizer component; and The emulsion contains 0.5% to 1.5% by weight of ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0345] In some embodiments, the emulsion comprises: about 45% to about 55% water by weight of the emulsion; an oil component of about 15% to about 24% by weight of the emulsion; an emulsifier component from about 4% to about 7% by weight of the emulsion; a solvent component of about 20% to about 25% by weight of the emulsion; about 0.3% to about 0.5% by weight of the emulsion of a stabilizer component; and The emulsion contains 0.5% to 1.5% by weight of ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0346] In some embodiments, the oil component comprises one or more materials independently selected from petrolatum, fatty alcohols, mineral oils, triglycerides, and dimethicone; the emulsifier component comprises one or more materials independently selected from glyceryl fatty acid esters and sorbitan fatty acid esters; the solvent component comprises one or more materials independently selected from alkylene glycols and polyalkylene glycols; The stabilizer component includes one or more materials independently selected from polysaccharides.

[0347] In some embodiments, the oil component comprises one or more materials independently selected from white petrolatum, cetyl alcohol, stearyl alcohol, light mineral oil, medium chain triglycerides, and dimethicone; the emulsifier component comprises one or more materials independently selected from glyceryl stearate and polysorbate 20; the solvent component comprises one or more materials independently selected from propylene glycol and polyethylene glycol; The stabilizer component includes xanthan gum.

[0348] In some embodiments, the emulsion comprises: about 35% to about 65% water by weight of the emulsion; about 2% to about 15% by weight of the emulsion of an occlusive agent component; about 2% to about 8% by weight of the emulsion of a hardener component; about 5% to about 15% by weight of the emulsion of an emollient component; from about 1% to about 9% by weight of the emulsion of an emulsifier component; about 0.05% to about 5% by weight of the emulsion of a stabilizer component; A solvent component of about 10% to about 35% by weight of the emulsion; and The emulsion contains 0.5% to 1.5% by weight of ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0349] In some embodiments, the emulsion comprises: about 40% to about 60% water by weight of the emulsion; an occlusive agent component, from about 5% to about 10% by weight of the emulsion; about 2% to about 8% by weight of the emulsion of a hardener component; about 7% to about 12% by weight of the emulsion of an emollient component; an emulsifier component, from about 2% to about 6% by weight of the emulsion; about 0.1% to about 2% by weight of the emulsion of a stabilizer; A solvent component of about 15% to about 30% by weight of the emulsion; and The emulsion contains 0.5% to 1.5% by weight of ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0350] In some embodiments, the emulsion comprises: about 45% to about 55% water by weight of the emulsion; an occlusive agent component, from about 5% to about 10% by weight of the emulsion; about 3% to about 6% by weight of the emulsion of a hardener component; about 7% to about 13% by weight of the emulsion of an emollient component; an emulsifier component, from about 3% to about 5% by weight of the emulsion; about 0.3% to about 0.5% by weight of the emulsion of a stabilizer component; A solvent component of about 20% to about 25% by weight of the emulsion; and The emulsion contains 0.5% to 1.5% by weight of ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0351] In some embodiments, the emulsion comprises: about 45% to about 55% water by weight of the emulsion; an occlusive agent component, from about 5% to about 10% by weight of the emulsion; about 4% to about 7% by weight of the emulsion of a hardener component; about 7% to about 13% by weight of the emulsion of an emollient component; an emulsifier component from about 4% to about 7% by weight of the emulsion; about 0.3% to about 0.5% by weight of the emulsion of a stabilizer component; A solvent component of about 20% to about 25% by weight of the emulsion; and The emulsion contains 0.5% to 1.5% by weight of ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0352] In some embodiments, the emulsion comprises: about 45% to about 55% water by weight of the emulsion; an occlusive agent component at about 7% by weight of the emulsion; about 4.5% to about 5% by weight of the emulsion of a hardener component; an emollient component at about 10% by weight of the emulsion; an emulsifier component, from about 4% to about 4.5% by weight of the emulsion; a stabilizer component at about 0.4% by weight of the emulsion; A solvent component of about 22% by weight of the emulsion; and The emulsion contains 0.5% to 1.5% by weight of ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0353] In some embodiments, ruxolitinib, or a pharma- ceutically acceptable salt thereof, is present as ruxolitinib phosphate.

[0354] In some embodiments, the emulsion comprises 1.5% ruxolitinib or a pharma- ceutically acceptable salt thereof by weight of the emulsion.

[0355] In some embodiments, the emulsion comprises 1.5% ruxolitinib phosphate by weight of the emulsion.

[0356] In some embodiments, the emulsion comprises 0.75% ruxolitinib or a pharma- ceutically acceptable salt thereof by weight of the emulsion.

[0357] In some embodiments, the emulsion comprises 0.75% ruxolitinib phosphate by weight of the emulsion.

[0358] In some embodiments, the combined amount of the hardener component and the emulsifier component is at least about 8% by weight of the emulsion.

[0359] In some embodiments, The occlusive agent component includes petrolatum, The hardener component comprises one or more materials independently selected from one or more fatty alcohols; the emollient component comprises one or more materials independently selected from mineral oil and triglycerides; the emulsifier component comprises one or more materials independently selected from glyceryl fatty acid esters and sorbitan fatty acid esters; The stabilizer component comprises one or more materials independently selected from polysaccharides; The solvent component comprises one or more materials independently selected from alkylene glycols and polyalkylene glycols.

[0360] In some embodiments, The occlusive agent component includes white petrolatum, the hardener component comprises one or more materials independently selected from cetyl alcohol and stearyl alcohol; the emollient component comprises one or more materials independently selected from light mineral oil, medium chain triglycerides, and dimethicone; the emulsifier component comprises one or more materials independently selected from glyceryl stearate and polysorbate 20; Stabilizer ingredients include xanthan gum, The solvent component includes one or more materials independently selected from propylene glycol and polyethylene glycol.

[0361] In some embodiments, the emulsion further comprises an antimicrobial preservative component.

[0362] In some embodiments, the antimicrobial preservative component is present in an amount from about 0.05% to about 3% by weight of the emulsion.

[0363] In some embodiments, the antimicrobial preservative component is present in an amount of about 0.1% to about 1% by weight of the emulsion.

[0364] In some embodiments, the antimicrobial preservative component comprises one or more materials independently selected from alkylparabens and phenoxyethanol.

[0365] In some embodiments, the antimicrobial preservative component comprises one or more materials independently selected from methylparaben, propylparaben, and phenoxyethanol.

[0366] In some embodiments, the emulsion further comprises a chelating agent component.

[0367] In some embodiments, the chelating agent component comprises edetate disodium.

[0368] Ruxolitinib can be prepared as described in U.S. Patent No. 7,598,257 and U.S. Patent Publication No. 2009 / 0181959, each of which is incorporated herein by reference in its entirety. The 1:1 phosphate salt of ruxolitinib can be prepared as described in U.S. Patent Publication No. 2008 / 0312259, which is incorporated herein by reference in its entirety.

[0369] As will be appreciated, some components of the creams (emulsions) described herein can have multiple functions. For example, a given substance may act as both an emulsifier component and a stabilizer. In such cases, the function of a particular component can be considered to be single, even if its properties allow for multiple functions. In some embodiments, each component of the formulation comprises a different substance or mixture of substances.

[0370] It will be further understood that certain features of the present disclosure, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the present disclosure, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination.

[0371] The following embodiments are provided:

[0372] 1. A method for relieving itch in a human patient having atopic dermatitis, comprising administering twice daily to the skin of said human patient in need thereof a cream formulation, said cream formulation comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis; The method, wherein the patient achieves a reduction in itch numerical rating scale score from baseline.

[0373] 2. The patient, Between 18 and 70 years old, Have been diagnosed with atopic dermatitis for at least 2 years IGA score of 2-3 at screening and baseline The method of embodiment 1, wherein the body surface area (excluding face and interstitial areas) involved in atopic dermatitis at baseline is between 3% and 20%.

[0374] 3. The method of embodiment 1 or 2, wherein the patient is diagnosed with atopic dermatitis as defined by the Hanifin and Radica criteria.

[0375] 4. The method of any one of embodiments 1-3, wherein said twice daily administrations are at least 8 hours apart.

[0376] 5. The method of any one of embodiments 1-4, wherein the cream formulation is an oil-in-water emulsion containing 1.5% (w / w) ruxolitinib phosphate on a free base basis.

[0377] 6. The method of any one of the preceding embodiments, wherein the cream formulation has a pH of about 2.8 to about 3.6.

[0378] 7. The method according to any one of the preceding embodiments, wherein said cream formulation is a solubilized cream.

[0379] 8. The method of any one of embodiments 1-7, wherein the patient achieves a statistically significant reduction in itch numerical rating scale score from baseline on the second day of the administration compared to patients administered a placebo for the same period of time.

[0380] 9. The method of any one of embodiments 1-8, wherein the patient achieves at least a 1.5 point reduction in itch numerical rating scale score from baseline on the second day of said administration.

[0381] 10. The method of any one of embodiments 1-9, wherein the patient achieves a statistically significant reduction in itch numerical rating scale score from baseline at week 2 of the administration compared to patients administered a placebo for the same period.

[0382] 11. The method of any one of embodiments 1-10, wherein the patient achieves at least a 3 point reduction in itch numerical rating scale score from baseline at the second week of said administration.

[0383] 12. The method of any one of embodiments 1-11, wherein the patient achieves a statistically significant reduction in itch numerical rating scale score from baseline at week 4 of the administration compared to patients administered a placebo for the same period.

[0384] 13. The method of any one of embodiments 1-12, wherein the patient achieves at least a 3 point reduction in itch numerical rating scale score from baseline at week 4 of the administration.

[0385] 14. The method of any one of embodiments 1-13, wherein the patient achieves a statistically significant reduction in itch numerical rating scale score from baseline at week 8 of the administration compared to patients administered a placebo for the same period.

[0386] 15. The method of any one of embodiments 1-14, wherein the patient achieves at least a 3 point reduction in itch numerical rating scale score from baseline at week 8 of the administration.

[0387] 16. The method of any one of embodiments 1-15, wherein the patient achieves at least a 4 point reduction in itch numerical rating scale score from baseline at week 8 of the administration.

[0388] 17. The method of any one of embodiments 1-16, wherein the patient achieves at least a 4.5 point reduction in itch numerical rating scale score from baseline at week 12 of the administration.

[0389] 18. The method of any one of embodiments 1-17, wherein said administering reverses symptoms of atopic dermatitis.

[0390] 19. The method of any one of embodiments 1-18, wherein the patient achieves a statistically significant improvement in Eczema Area and Severity Index score from baseline at week 4 of the administration compared to patients administered a placebo for the same period.

[0391] 20. The method of any one of embodiments 1-19, wherein the patient achieves a statistically significant improvement in Eczema Area and Severity Index score from baseline at week 8 of the administration compared to patients administered a placebo for the same period.

[0392] 21. The method of any one of embodiments 1-20, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 2 of the administration.

[0393] 22. The method of any one of embodiments 1-21, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 4 of the administration.

[0394] 23. The method of any one of embodiments 1-22, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 8 of the administration.

[0395] 24. The method of any one of embodiments 1-23, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 12 of the administration.

[0396] 25. The method of any one of embodiments 1-24, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 2 weeks of administration.

[0397] 26. The method of any one of embodiments 1-25, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 4 weeks of administration.

[0398] 27. The method of any one of embodiments 1-26, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of administration.

[0399] 28. The method of any one of embodiments 1-27, wherein the patient achieves a clinically meaningful improvement in the PROMIS Short Form-Sleep Disorders (8b) 24-hour recall score at Week 8.

[0400] 29. The method of any one of embodiments 1-28, wherein said administration is maintained for at least 2 weeks.

[0401] 30. The method of any one of embodiments 1-29, wherein said administration is maintained for at least 4 weeks.

[0402] 31. The method of any one of embodiments 1-30, wherein said administration is maintained for at least 8 weeks.

[0403] 32. The method of any one of embodiments 1-31, wherein said administration is maintained for at least 12 weeks.

[0404] 33. The method of any one of embodiments 1-32, wherein the patient has not used any topical treatment for atopic dermatitis other than a mild emollient within 2 weeks of baseline, and has not used any systemic immunosuppressants or systemic immunomodulatory agents within 4 weeks of baseline.

[0405] 34. The method of any one of embodiments 1 to 33, wherein the patient is not receiving other therapeutic agents used to treat atopic dermatitis.

[0406] 35. A method for relieving itch in a human patient having atopic dermatitis, comprising administering a cream formulation to the skin of the human patient in need thereof twice daily, wherein the cream formulation is an oil-in-water emulsion containing 1.5% (w / w) ruxolitinib phosphate on a free base basis; said administration being maintained for at least 8 weeks; the patient achieves at least a 4 point reduction in itch NRS score from baseline at week 8 of the administration; The method, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2 point improvement from baseline at 8 weeks of the administration.

[0407] 36. The method of embodiment 35, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of administration.

[0408] 37. The patient, Between 18 and 70 years old, Have been diagnosed with atopic dermatitis for at least 2 years IGA score of 2-3 at screening and baseline The method of embodiment 35 or 36, wherein the body surface area (excluding face and interstitial areas) involved in atopic dermatitis at baseline is between 3% and 20%.

[0409] 38. A method for relieving itch in a human patient having atopic dermatitis, comprising administering twice daily to the skin of the human patient in need thereof a cream formulation, the cream formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis; The method, wherein the patient achieves a reduction in itch numerical rating scale score from baseline.

[0410] 39. A method for relieving itch in a human patient having atopic dermatitis, comprising administering twice daily to the skin of the human patient in need thereof a cream formulation, the cream formulation comprising 0.75% (w / w) of ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis; The method, wherein the patient achieves a reduction in itch numerical rating scale score from baseline.

[0411] 40. The method of embodiment 38 or 39, wherein said ruxolitinib or a pharma- ceutically acceptable salt thereof is ruxolitinib phosphate.

[0412] 41. The patient, Between 18 and 70 years old, Have been diagnosed with atopic dermatitis for at least 2 years Investigator Global Assessment score was 2-3 at screening and baseline; The method of any one of embodiments 38-40, wherein the body surface area (excluding face and interstitial areas) involved in atopic dermatitis at baseline is between 3% and 20%.

[0413] 42. The method of any one of embodiments 38 to 41, wherein the patient is diagnosed with atopic dermatitis as defined by the Hanifin and Rajka criteria.

[0414] 43. The method of any one of embodiments 38-42, wherein the patient achieves at least a 4-point improvement in itch numerical rating scale score improvement from baseline.

[0415] 44. The method of any one of embodiments 38-43, wherein the patient achieves at least a 4 point improvement in itch numerical rating scale score improvement from baseline, and the patient has a baseline numerical rating scale score of 4 or greater.

[0416] 45. The method of any one of embodiments 38-44, wherein the patient achieves at least a 4-point improvement in itch numerical rating scale score improvement from baseline 2 weeks after the administration, and the patient has a baseline numerical rating scale score of 4 or greater.

[0417] 46. ​​The method of any one of embodiments 38-45, wherein the patient achieves at least a 4-point improvement in itch numerical rating scale score improvement from baseline 4 weeks after the administration, and the patient has a baseline numerical rating scale score of 4 or greater.

[0418] 47. The method of any one of embodiments 38-46, wherein the patient achieves at least a 4-point improvement in itch numerical rating scale score improvement from baseline after 8 weeks of said administration, and the patient has a baseline numerical rating scale score of 4 or greater.

[0419] 48. The method of any one of embodiments 38-47, wherein the patient achieves at least a 2-point improvement in itch numerical rating scale score from baseline on the second day of the administration.

[0420] 49. The method of any one of embodiments 38-49, wherein the patient achieves rapid relief from itch.

[0421] 50. The method of any one of embodiments 38-49, wherein the patient achieves a statistically significant reduction in itch on the first day of said administration.

[0422] 51. The method of any one of embodiments 38-50, wherein the patient achieves a statistically significant reduction in itch numerical rating scale score from baseline on day 1 of the administration compared to patients administered a placebo for the same period of time.

[0423] 52. The method of any one of embodiments 38-51, wherein the patient achieves at least a 1-point reduction in itch numerical rating scale score from baseline on the first day of the administration.

[0424] 53. The method of any one of embodiments 38-52, wherein the patient achieves a statistically significant reduction in itch numerical rating scale score from baseline on day 1 of the administration compared to patients administered a placebo for the same period of time.

[0425] 54. The method of any one of embodiments 38-53, wherein the patient achieves at least a 2-point reduction in itch numerical rating scale score from baseline on the second day of the administration.

[0426] 55. The method of any one of embodiments 38-54, wherein the patient achieves at least a 3 point reduction in itch numerical rating scale score from baseline at the second week of the administration.

[0427] 56. The method of any one of embodiments 38-55, wherein the patient achieves at least a 3-point reduction in itch numerical rating scale score from baseline at week 4 of the administration.

[0428] 57. The method of any one of embodiments 38-56, wherein the patient achieves at least a 3-point reduction in itch numerical rating scale score from baseline at week 8 of the administration.

[0429] 58. The method of any one of embodiments 38-57, wherein the patient achieves at least a 4 point reduction in itch numerical rating scale score from baseline at the second week of the administration.

[0430] 59. The method of any one of embodiments 38-58, wherein the patient achieves at least a 4 point reduction in itch numerical rating scale score from baseline at week 4 of the administration.

[0431] 60. The method of any one of embodiments 38-59, wherein the patient achieves at least a 4 point reduction in itch numerical rating scale score from baseline at week 8 of the administration.

[0432] 61. The method of any one of embodiments 38-60, wherein said administering reverses symptoms of atopic dermatitis.

[0433] 62. The method of any one of embodiments 38-61, wherein the patient achieves a statistically significant improvement in Eczema Area and Severity Index score from baseline at week 4 of the administration compared to patients administered a placebo for the same period.

[0434] 63. The method of any one of embodiments 38-62, wherein the patient achieves a statistically significant improvement in Eczema Area and Severity Index score from baseline at week 8 of the administration compared to patients administered a placebo for the same period.

[0435] 64. The method of any one of embodiments 38-63, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 2 of the administration.

[0436] 65. The method of any one of embodiments 38-64, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 4 of the administration.

[0437] 66. The method of any one of embodiments 38-65, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 8 of the administration.

[0438] 67. The method of any one of embodiments 38-66, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 12 of the administration.

[0439] 68. The method of any one of embodiments 38-67, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 2 weeks of administration.

[0440] 69. The method of any one of embodiments 38-68, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 4 weeks of administration.

[0441] 70. The method of any one of embodiments 38-69, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of administration.

[0442] 71. The method of any one of embodiments 38-71, wherein the patient achieves a clinically meaningful improvement in the PROMIS Short Form-Sleep Disorders (8b) 24-hour recall score at Week 8.

[0443] 72. The method of any one of embodiments 38-71, wherein said administration is maintained for at least 2 weeks.

[0444] 73. The method of any one of embodiments 38-72, wherein said administration is maintained for at least 4 weeks.

[0445] 74. The method of any one of embodiments 38-73, wherein said administration is maintained for at least 8 weeks.

[0446] 75. The method of any one of embodiments 38-74, wherein said administration is maintained for at least 12 weeks.

[0447] 76. The method of any one of embodiments 38-75, wherein the patient has not used any topical treatment for atopic dermatitis other than a mild emollient within 2 weeks of baseline and has not used any systemic immunosuppressants or systemic immunomodulatory agents within 4 weeks of baseline.

[0448] 77. The method of any one of embodiments 38-76, wherein the patient is not receiving other therapeutic agents used to treat atopic dermatitis.

[0449] 78. The method of any one of embodiments 38-77, wherein said administration of said cream formulation does not result in a statistically significant decrease in hemoglobin or platelets.

[0450] 79. The method of any one of embodiments 38-78, wherein said administration of said cream formulation does not result in burning at the site of administration.

[0451] 80. The method of any one of embodiments 38-79, wherein the cream formulation is an oil-in-water emulsion comprising the ruxolitinib, or a pharma- ceutically acceptable salt thereof.

[0452] 81. The method of any one of embodiments 38-80, wherein the cream formulation has a pH of about 2.8 to about 3.6.

[0453] 82. The method of any one of embodiments 38-81, wherein the cream formulation is a solubilized cream.

[0454] 83. The method of any one of embodiments 38-82, wherein the twice daily administration is at least 8 hours apart.

[0455] 84. A method for relieving itch in a human patient with atopic dermatitis, comprising administering a cream formulation to the skin of the human patient in need thereof twice daily, wherein the cream formulation is an oil-in-water emulsion containing 1.5% (w / w) ruxolitinib phosphate on a free base basis; said administration being maintained for at least 8 weeks; the patient achieves at least a 4 point reduction in itch NRS score from baseline at week 8 of the administration; The method, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2 point improvement from baseline at 8 weeks of the administration.

[0456] 85. The method of embodiment 84, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of administration.

[0457] 86. The patient, Between 18 and 70 years old, Have been diagnosed with atopic dermatitis for at least 2 years Investigator Global Assessment score was 2-3 at screening and baseline; The method of embodiment 84 or 85, wherein the body surface area (excluding face and interstitial areas) involved in atopic dermatitis at baseline is between 3% and 20%.

[0458] 87. A method for treating atopic dermatitis in a human patient in need thereof, comprising administering a cream formulation to the skin of the human patient twice daily, wherein the cream formulation comprises 0.75% (w / w) of ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0459] 88. The method of embodiment 87, wherein said ruxolitinib or a pharma- ceutically acceptable salt thereof is ruxolitinib phosphate.

[0460] 89. The method of any one of embodiments 87-88, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline.

[0461] 90. The method of any one of embodiments 87-89, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 2 weeks of administration.

[0462] 91. The method of any one of embodiments 87-90, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 4 weeks of administration.

[0463] 92. The method of any one of embodiments 87-91, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of administration.

[0464] 93. The method of any one of embodiments 87-92, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline.

[0465] 94. The method of any one of embodiments 87-93, wherein the patient achieves a statistically significant improvement in Eczema Area and Severity Index score from baseline at week 4 of the administration compared to patients administered a placebo for the same period.

[0466] 95. The method of any one of embodiments 87-94, wherein the patient achieves a statistically significant improvement in Eczema Area and Severity Index score from baseline at week 8 of the administration compared to patients administered a placebo for the same period.

[0467] 96. The method of any one of embodiments 87-95, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at the second week of said administration.

[0468] 97. The method of any one of embodiments 87-96, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 4 of the administration.

[0469] 98. The method of any one of embodiments 87-97, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 8 of the administration.

[0470] 99. The method of any one of embodiments 87-98, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 12 of the administration.

[0471] 100. The method of any one of embodiments 87-99, wherein the patient achieves a clinically meaningful improvement in the PROMIS Short Form-Sleep Disorders (8b) 24-hour recall score.

[0472] 101. The method of any one of embodiments 87-100, wherein the patient achieves a clinically meaningful improvement in the PROMIS Short Form-Sleep Disorders (8b) 24-hour recall score at Week 8.

[0473] 102. The method of any one of embodiments 87-101, wherein said administration is maintained for at least 2 weeks.

[0474] 103. The method of any one of embodiments 87-102, wherein said administration is maintained for at least 4 weeks.

[0475] 104. The method of any one of embodiments 87-103, wherein said administration is maintained for at least 8 weeks.

[0476] 105. The method of any one of embodiments 87-104, wherein said administration is maintained for at least 12 weeks.

[0477] 106. The method of any one of embodiments 87-105, wherein the patient has not used any topical treatment for atopic dermatitis other than a mild emollient within 2 weeks of baseline, and has not used any systemic immunosuppressants or systemic immunomodulatory agents within 4 weeks of baseline.

[0478] 107. The method of any one of embodiments 87-106, wherein the patient is not receiving other therapeutic agents used to treat atopic dermatitis.

[0479] 108. The method of any one of embodiments 87-107, wherein the twice daily administrations are at least 8 hours apart.

[0480] 109. The method of any one of embodiments 87-108, wherein the cream formulation is an oil-in-water emulsion containing 0.75% (w / w) ruxolitinib phosphate on a free base basis.

[0481] 110. The method of any one of embodiments 87-109, wherein the cream formulation has a pH of about 2.8 to about 3.6.

[0482] 111. The method of any one of embodiments 87-110, wherein the cream formulation is a solubilized cream.

[0483] 112. The patient, Between 18 and 70 years old, Have been diagnosed with atopic dermatitis for at least 2 years Investigator Global Assessment score was 2-3 at screening and baseline; The method of any one of embodiments 87-111, wherein the body surface area (excluding face and interstitial areas) involved in atopic dermatitis at baseline is between 3% and 20%.

[0484] 113. The method of any one of embodiments 87 to 112, wherein the patient is diagnosed with atopic dermatitis as defined by the Hanifin and Rajka criteria.

[0485] 114. The method of any one of embodiments 87-113, wherein the patient achieves at least a 4-point improvement in itch numerical rating scale score improvement from baseline.

[0486] 115. The method of any one of embodiments 87-114, wherein the patient achieves at least a 4 point improvement in itch numerical rating scale score improvement from baseline, and the patient has a baseline numerical rating scale score of 4 or greater.

[0487] 116. The method of any one of embodiments 87-115, wherein the patient achieves at least a 4-point improvement in itch numerical rating scale score improvement from baseline 2 weeks after the administration, and the patient has a baseline numerical rating scale score of 4 or greater.

[0488] 117. The method of any one of embodiments 87-116, wherein the patient achieves at least a 4-point improvement in itch numerical rating scale score improvement from baseline 4 weeks after the administration, and the patient has a baseline numerical rating scale score of 4 or greater.

[0489] 118. The method of any one of embodiments 87-117, wherein the patient achieves at least a 4-point improvement in itch numerical rating scale score improvement from baseline 8 weeks after the administration, and the patient has a baseline numerical rating scale score of 4 or greater.

[0490] 119. The method of any one of embodiments 87-118, wherein the patient achieves at least a 2-point improvement in itch numerical rating scale score from baseline on the second day of the administration.

[0491] 120. The method of any one of embodiments 87-119, wherein said administration of said cream formulation does not result in a statistically significant decrease in hemoglobin or platelets.

[0492] 121. The method of any one of embodiments 87-120, wherein said administration of said cream formulation does not result in burning at the site of administration.

[0493] 122. A method for treating moderate atopic dermatitis in a human patient in need thereof, comprising administering a topical formulation to the skin of the human patient twice daily, wherein the topical formulation comprises 0.75% (w / w) or 1.5% (w / w) of ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis.

[0494] 123. A method for treating moderate to severe atopic dermatitis in a human patient in need thereof, comprising administering a topical formulation to the skin of the human patient twice daily, wherein the topical formulation comprises 0.75% (w / w) or 1.5% (w / w) of ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis.

[0495] 124. A method of treating atopic dermatitis in a human patient in need thereof, comprising administering a topical formulation to the skin of the human patient twice daily, wherein the topical formulation comprises 0.75% (w / w) or 1.5% (w / w) of ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis; The patient is A baseline Eczema Area and Severity Index score of 16 or greater, and The method, wherein the body surface area involved by atopic dermatitis at baseline is 10% or more.

[0496] 125. The method of any one of embodiments 122-124, wherein the topical formulation is a cream formulation.

[0497] 126. The method according to any one of embodiments 122 to 125, wherein the formulation comprises 0.75% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0498] 127. The method according to any one of embodiments 122 to 125, wherein the formulation comprises 1.5% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0499] 128. The method of any one of embodiments 122 to 125, wherein the formulation comprises 0.75% (w / w) ruxolitinib phosphate on a free base basis.

[0500] 129. The method of any one of embodiments 122 to 125, wherein the formulation comprises 1.5% (w / w) ruxolitinib phosphate on a free base basis.

[0501] 130. The method of any one of embodiments 122-129, wherein the patient has an Itch Numeric Rating Scale score of 4 or greater at baseline.

[0502] 131. The method of any one of embodiments 122-130, wherein the patient has an Investigator's Global Assessment score of 3 at baseline.

[0503] 132. The method of any one of embodiments 122-130, wherein the patient has an Investigator's Global Assessment score of 3-4 at baseline.

[0504] 133. The patient, Investigator's Global Assessment score of 3 at baseline; The method of any one of embodiments 122-129, wherein the baseline Itch Numeric Rating Scale score is 4 or greater.

[0505] 134. The patient, Investigator's Global Assessment score of 3-4 at baseline The method of any one of embodiments 122-129, wherein the baseline Itch Numeric Rating Scale score is 4 or greater.

[0506] 135. The method of any one of embodiments 122-134, wherein the patient is 12 years of age or older.

[0507] 136. The method of any one of embodiments 122 to 135, wherein the patient has a history of atopic dermatitis for at least 2 years.

[0508] 137. The patient, Investigator's Global Assessment score of 3 at baseline; Have a history of atopic dermatitis for at least 2 years The method of any one of embodiments 122-129, wherein the patient is 12 years of age or older.

[0509] 138. The patient, Investigator's Global Assessment score of 3-4 at baseline Have a history of atopic dermatitis for at least 2 years The method of any one of embodiments 122-129, wherein the patient is 12 years of age or older.

[0510] 139. The patient, Investigator's Global Assessment score of 3 at baseline; had a baseline itch numeric rating scale score of 4 or higher; Have a history of atopic dermatitis for at least 2 years The method of any one of embodiments 122-129, wherein the patient is 12 years of age or older.

[0511] 140. The patient, Investigator's Global Assessment score of 3-4 at baseline had a baseline itch numeric rating scale score of 4 or higher; Have a history of atopic dermatitis for at least 2 years The method of any one of embodiments 122-129, wherein the patient is 12 years of age or older.

[0512] 141. The patient has the following characteristics: Characteristics with an Investigator Global Assessment score of 3 at baseline, Characterized by a baseline itch numeric rating scale score of 4 or higher; Characterized by a history of atopic dermatitis for at least 2 years, and The method of any one of embodiments 122-129, wherein the subject has one or more of the following characteristics: being 12 years of age or older.

[0513] 142. The patient has the following characteristics: Characteristics of baseline Investigator Global Assessment score of 3–4; Characterized by a baseline itch numeric rating scale score of 4 or higher; Characterized by a history of atopic dermatitis for at least 2 years, and The method of any one of embodiments 122-129, wherein the subject has one or more of the following characteristics: being 12 years of age or older.

[0514] 143. The method of any one of embodiments 122 to 142, wherein the patient is diagnosed with atopic dermatitis as defined by the Hanifin and Rajka criteria.

[0515] 144. The method of any one of embodiments 122-143, wherein said administration is maintained for at least 2 weeks.

[0516] 145. The method of any one of embodiments 122-143, wherein said administration is maintained for at least 4 weeks.

[0517] 146. The method of any one of embodiments 122-143, wherein said administration is maintained for at least 8 weeks.

[0518] 147. The method of any one of embodiments 122-146, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline.

[0519] 148. The method of any one of embodiments 122-146, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 2 weeks of administration.

[0520] 149. The method of any one of embodiments 122-146, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 4 weeks of administration.

[0521] 150. The method of any one of embodiments 122-146, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at 8 weeks of administration.

[0522] 151. The method of any one of embodiments 122-150, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline.

[0523] 152. The method of any one of embodiments 122-151, wherein the patient achieves a statistically significant improvement in Eczema Area and Severity Index score from baseline at week 4 of the administration compared to patients administered a placebo for the same period.

[0524] 153. The method of any one of embodiments 122-152, wherein the patient achieves a statistically significant improvement in Eczema Area and Severity Index score from baseline at week 8 of the administration compared to patients administered a placebo for the same period.

[0525] 154. The method of any one of embodiments 122-153, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at the second week of said administration.

[0526] 155. The method of any one of embodiments 122-153, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 4 of the administration.

[0527] 156. The method of any one of embodiments 122-153, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 8 of the administration.

[0528] 157. The method of any one of embodiments 122-156, wherein the patient achieves at least a 4 point improvement in itch numerical rating scale score improvement from baseline, and the patient has a baseline numerical rating scale score of 4 or greater.

[0529] 158. The method of any one of embodiments 122-156, wherein the patient achieves at least a 4-point improvement in itch numerical rating scale score improvement from baseline 2 weeks after the administration, and the patient has a baseline numerical rating scale score of 4 or greater.

[0530] 159. The method of any one of embodiments 122-156, wherein the patient achieves at least a 4-point improvement in itch numerical rating scale score improvement from baseline 4 weeks after the administration, and the patient has a baseline numerical rating scale score of 4 or greater.

[0531] 160. The method of any one of embodiments 122-156, wherein the patient achieves at least a 4-point improvement in itch numerical rating scale score improvement from baseline after 8 weeks of said administration, and the patient has a baseline numerical rating scale score of 4 or greater.

[0532] 161. The method of any one of embodiments 122-160, wherein the patient achieves at least a 2-point improvement in itch numerical rating scale score from baseline on the second day of the administration.

[0533] 162. The method of any one of embodiments 122-161, wherein the patient achieves a clinically meaningful improvement in the PROMIS Short Form-Sleep Disorders (8b) 24-hour recall score.

[0534] 163. The method of any one of embodiments 122-162, wherein the patient achieves a clinically meaningful improvement in the PROMIS Short Form-Sleep Disorders (8b) 24-hour recall score at week 8.

[0535] 164. The patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 4 of the administration; and The method of any one of embodiments 122-143, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2 point improvement from baseline at week 4 of said administration.

[0536] 165. The patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of the administration; and The method of any one of embodiments 122-143, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at week 8 of the administration.

[0537] 166. The patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 4 of the administration; and The method of any one of embodiments 122-143, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 4 of the administration.

[0538] 167. The patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of the administration; and The method of any one of embodiments 122-143, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 8 of the administration.

[0539] 168. The patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at week 4 of the treatment; and The method of any one of embodiments 122-143, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 4 of the administration.

[0540] 169. The patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at week 8 of the treatment; and The method of any one of embodiments 122-143, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 8 of the administration.

[0541] 170. The patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 4 of the administration; The patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at week 4 of the administration; and The method of any one of embodiments 122-143, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 4 of the administration.

[0542] 171. The patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of the administration; The patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at week 8 of the administration; and The method of any one of embodiments 122-143, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 8 of the administration.

[0543] 172. The method of any one of embodiments 122-171, wherein the patient has not used any topical treatment for atopic dermatitis other than a mild emollient within 2 weeks of baseline, and has not used any systemic immunosuppressants or systemic immunomodulatory agents within 4 weeks of baseline.

[0544] 173. The method of any one of embodiments 122-172, wherein the patient is not receiving other therapeutic agents used to treat atopic dermatitis.

[0545] 174. The method of any one of embodiments 122-173, wherein the two daily administrations are at least 8 hours apart.

[0546] 175. The method of any one of embodiments 122-174, wherein the cream formulation has a pH of about 2.8 to about 3.9.

[0547] 176. The method of any one of embodiments 122-174, wherein the cream formulation has a pH of about 2.8 to about 3.6.

[0548] 177. The method of any one of embodiments 122-176, wherein the cream formulation is a solubilized cream.

[0549] 178. The method of any one of embodiments 122-177, wherein said administration of said preparation does not result in a statistically significant decrease in hemoglobin or platelets.

[0550] 179. The method of any one of embodiments 122-178, wherein said administration of said formulation does not result in burning at the administration site.

[0551] 180. A method for treating moderate atopic dermatitis in a human patient in need thereof, comprising administering a topical formulation to the skin of the human patient twice daily, wherein the topical formulation comprises 1.5% (w / w) ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis.

[0552] 181. The method of embodiment 180, wherein said ruxolitinib or a pharma- ceutically acceptable salt thereof is ruxolitinib phosphate.

[0553] 182. The method of embodiment 180, wherein the patient is 12 years of age or older.

[0554] 183. The method of embodiment 180, wherein the patient has 10% to 20% of body surface area involved in atopic dermatitis at baseline.

[0555] 184. The method of embodiment 180, wherein the patient has an Eczema Area and Severity Index score of 16 or greater at baseline.

[0556] 185. The method of embodiment 180, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline.

[0557] 186. The method of embodiment 180, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline.

[0558] 187. The method of embodiment 180, wherein the patient achieves at least a 4-point improvement in itch numeric rating scale score improvement from baseline, and the patient has a baseline numeric rating scale score of 4 or greater.

[0559] 188. The patient, Achieving an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline; achieve at least a 4 point improvement in itch numeric rating scale score improvement from baseline, said patient having a baseline numeric rating scale score of 4 or greater; The method of embodiment 180, wherein the method achieves a 75% improvement in Eczema Area and Severity Index score from baseline.

[0560] 189. The patient, Achieved an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at Week 4; achieve at least a 4 point improvement in itch numeric rating scale score improvement from baseline at week 4, said patient having a baseline numeric rating scale score of 4 or greater; The method of embodiment 180, wherein the method achieves a 75% improvement in Eczema Area and Severity Index score from baseline at Week 4.

[0561] 190. The patient, Achieved an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at week 8; achieve at least a 4 point improvement in itch numeric rating scale score improvement from baseline at week 8, said patient having a baseline numeric rating scale score of 4 or greater; The method of embodiment 180, wherein the method achieves a 75% improvement in Eczema Area and Severity Index score from baseline at Week 8.

[0562] 191. The method of embodiment 180, wherein the patient achieves at least a 2-point improvement in itch numerical rating scale score from baseline on the second day of the administration.

[0563] 192. The method of embodiment 180, wherein the patient achieves a clinically meaningful improvement in the PROMIS Short Form-Sleep Disorders (8b) 24-hour recall score at week 8.

[0564] 193. The method of embodiment 180, wherein the formulation is a cream formulation.

[0565] 194. The method of embodiment 193, wherein the cream formulation is an oil-in-water emulsion.

[0566] 195. The method of embodiment 194, wherein the cream formulation has a pH of about 2.8 to about 3.9.

[0567] 196. The method of embodiment 195, wherein said administration of said preparation does not result in a statistically significant decrease in hemoglobin or platelets.

[0568] 197. The method of embodiment 196, wherein the administration of the formulation does not result in burning at the administration site.

[0569] 198. A method of treating atopic dermatitis in a human patient in need thereof comprising administering a topical formulation to the skin of the human patient twice daily, the topical formulation comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis, and the patient is Are 12 years of age or older; 10% to 20% of body surface area involved in atopic dermatitis at baseline, and The method, wherein the Investigator's Global Assessment score at baseline is 3.

[0570] 199. The method of embodiment 198, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline.

[0571] 200. The method of embodiment 198, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline.

[0572] 201. The method of embodiment 198, wherein the patient achieves at least a 4 point improvement in itch numeric rating scale score improvement from baseline, and the patient has a baseline numeric rating scale score of 4 or greater.

[0573] 202. The patient is Achieving an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline; achieve at least a 4 point improvement in itch numeric rating scale score improvement from baseline, said patient having a baseline numeric rating scale score of 4 or greater; The method of embodiment 198, wherein the method achieves a 75% improvement in Eczema Area and Severity Index score from baseline.

[0574] 203. The patient is Achieved an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at Week 4; achieve at least a 4 point improvement in itch numeric rating scale score improvement from baseline at week 4, said patient having a baseline numeric rating scale score of 4 or greater; The method of embodiment 198, wherein the method achieves a 75% improvement in Eczema Area and Severity Index score from baseline at Week 4.

[0575] 204. The patient is Achieved an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at week 8; achieve at least a 4 point improvement in itch numeric rating scale score improvement from baseline at week 8, said patient having a baseline numeric rating scale score of 4 or greater; The method of embodiment 198, wherein the method achieves a 75% improvement in Eczema Area and Severity Index score from baseline at Week 8.

[0576] 205. The method of embodiment 198, wherein the formulation is a cream formulation.

[0577] 206. The method of embodiment 205, wherein the cream formulation is an oil-in-water emulsion.

[0578] 207. A method for relieving itch in a human patient having atopic dermatitis, comprising administering twice daily to the skin of the human patient in need thereof a cream formulation, the cream formulation comprising 1.5% (w / w) of ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis; The method, wherein the patient achieves a statistically significant reduction in itch numerical rating scale score from baseline within 36 hours of the administration.

[0579] 208. A method for reducing itch in a human patient with atopic dermatitis, comprising administering twice daily to the skin of said human patient in need thereof a cream formulation comprising 1.5% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis, wherein said patient achieves at least a 1-point reduction in itch numerical rating scale score by the second day of said administration.

[0580] 209. The method of embodiment 208, wherein said ruxolitinib or a pharma- ceutically acceptable salt thereof is ruxolitinib phosphate.

[0581] 210. The method of embodiment 208, wherein said patient achieves a statistically significant reduction in itch numerical rating scale score from baseline within 12 hours of said administration.

[0582] 211. The method of embodiment 208, wherein the patient achieves a 2-point improvement in Itch Numeric Rating Scale score within 12 hours of the administration.

[0583] 212. The method of embodiment 208, wherein the patient achieves a 2-point improvement in Itch Numeric Rating Scale score within 36 hours of administering.

[0584] 213. The method of embodiment 208, wherein the patient achieves a 4-point improvement in Itch Numeric Rating Scale score within 36 hours of the administration.

[0585] 214. The method of embodiment 208, wherein the patient achieves at least a 2-point reduction in the Itch Numeric Rating Scale score during the first week of administration.

[0586] 215. The method of embodiment 208, wherein the patient achieves at least a 3 point reduction in the Itch Numeric Rating Scale score at the third week of the administration.

[0587] 216. The method of embodiment 208, wherein the patient achieves a minimal clinically important difference in itch numeric rating scale score within 36 hours of administering, wherein the minimal clinically important difference in itch numeric rating scale score is a 2 to 3 point reduction in itch numeric rating scale score compared to baseline, and wherein the patient has a baseline numeric rating scale score of 2 or greater.

[0588] 217. The method of embodiment 208, wherein the patient achieves a clinically relevant improvement in itch numeric rating scale score within 36 hours of administering, wherein the clinically relevant improvement in itch numeric rating scale score is a reduction of 4 or more points in the itch numeric rating scale score compared to baseline, and wherein the patient has a baseline numeric rating scale score of 4 or more.

[0589] 218. The method of embodiment 208, wherein the patient is 12 years of age or older.

[0590] 219. The method of embodiment 218, wherein the patient has a body surface area (BSA) (excluding scalp) involved in atopic dermatitis at baseline of 3% to 20%.

[0591] 220. The method of embodiment 219, wherein the patient has an Investigator's Global Assessment score of 2 to 3 at baseline.

[0592] 221. The method of embodiment 220, wherein the patient has been diagnosed with atopic dermatitis for at least 2 years.

[0593] 222. The method of embodiment 221, wherein the patient is diagnosed with atopic dermatitis as defined by the Hanifin and Rajka criteria.

[0594] 223. The method of embodiment 222, wherein the patient has not used a topical treatment for atopic dermatitis other than an emollient within 2 weeks of baseline.

[0595] 224. The method of embodiment 208, wherein the patient achieves at least a 4 point reduction in itch numerical rating scale score from baseline during the second week of the administration.

[0596] 225. The method of embodiment 208, wherein the patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 4 of the administration.

[0597] 226. The method of embodiment 208, wherein the patient achieves at least a 4-point reduction in itch numerical rating scale score from baseline at week 8 of the administration.

[0598] 227. The method of embodiment 208, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at the second week of said administration.

[0599] 228. The method of embodiment 208, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 4 of the administration.

[0600] 229. The method of embodiment 208, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 8 of the administration.

[0601] 230. The method of embodiment 208, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at week 2 of the administration.

[0602] 231. The method of embodiment 208, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at week 4 of the administration.

[0603] 232. The method of embodiment 208, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at week 8 of the administration.

[0604] 233. The method of embodiment 209, wherein the cream formulation is an oil-in-water emulsion.

[0605] 234. The method of embodiment 233, wherein the cream formulation has a pH of about 2.8 to about 3.6.

[0606] 235. A method for relieving itch in a human patient having atopic dermatitis, comprising administering twice daily to the skin of the human patient in need thereof a cream formulation, the cream formulation comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis; The patient is Are 12 years of age or older; Investigator's Global Assessment score of 2-3 at baseline Baseline atopic dermatitis involvement between 3% and 20% of the body surface area (excluding scalp); and The method of claim 1, wherein a minimal clinically important difference in itch numeric rating scale score is achieved within 36 hours of said administration, said minimal clinically important difference in itch numeric rating scale score being a 2 to 3 point reduction in itch numeric rating scale score compared to baseline, and said patient having a baseline itch numeric rating scale score of 2 or greater.

[0607] 236. A method for relieving itch in a human patient having atopic dermatitis, comprising administering twice daily to the skin of the human patient in need thereof a cream formulation, the cream formulation comprising 1.5% (w / w) ruxolitinib phosphate on a free base basis; The patient is Are 12 years of age or older; Investigator's Global Assessment score of 2-3 at baseline Baseline atopic dermatitis involvement between 3% and 20% of the body surface area (excluding scalp); and The method, wherein the patient achieves a clinically relevant improvement in itch numeric rating scale score within 36 hours of administering, wherein the clinically relevant improvement in itch numeric rating scale score is a reduction in itch numeric rating scale score of 4 or more points compared to baseline, and the patient has a baseline numeric rating scale score of 4 or greater.

[0608] 237. A method for treating atopic dermatitis in a human patient in need thereof, comprising administering a cream formulation to the skin of the human patient twice daily, wherein the cream formulation comprises 0.75% (w / w) of ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

[0609] 238. The method of embodiment 237, wherein said ruxolitinib or a pharma- ceutically acceptable salt thereof is ruxolitinib phosphate.

[0610] 239. The method of embodiment 237, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline.

[0611] 240. The method of embodiment 237, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at week 2 of the administration.

[0612] 241. The method of embodiment 237, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at week 4 of the administration.

[0613] 242. The method of embodiment 237, wherein the patient achieves an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement from baseline at week 8 of the administration.

[0614] 243. The method of embodiment 237, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline.

[0615] 244. The method of embodiment 237, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at the second week of said administration.

[0616] 245. The method of embodiment 237, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 4 of the administration.

[0617] 246. The method of embodiment 237, wherein the patient achieves a 75% improvement in Eczema Area and Severity Index score from baseline at week 8 of the administration.

[0618] 247. The method of embodiment 237, wherein the patient achieves at least a 4-point improvement in itch numerical rating scale score improvement from baseline.

[0619] 248. The method of embodiment 237, wherein the patient achieves at least a 4-point improvement in itch numeric rating scale score improvement from baseline, and the patient has a baseline numeric rating scale score of 4 or greater.

[0620] 249. The method of embodiment 237, wherein the patient achieves at least a 4-point improvement in itch numeric rating scale score improvement from baseline at week 2 of the administration, and the patient has a baseline numeric rating scale score of 4 or greater.

[0621] 250. The method of embodiment 237, wherein the patient achieves at least a 4-point improvement in itch numeric rating scale score improvement from baseline at week 4 of the administration, and the patient has a baseline numeric rating scale score of 4 or greater.

[0622] 251. The method of embodiment 237, wherein the patient achieves at least a 4-point improvement in itch numeric rating scale score improvement from baseline at week 8 of the administration, and the patient has a baseline numeric rating scale score of 4 or greater.

[0623] 252. The method of embodiment 237, wherein the patient achieves a minimal clinically important difference in itch numeric rating scale score within 36 hours of administering, wherein the minimal clinically important difference in itch numeric rating scale score is a 2 to 3 point reduction in itch numeric rating scale score compared to baseline, and wherein the patient has a baseline numeric rating scale score of 2 or greater.

[0624] 253. The method of embodiment 237, wherein the patient achieves a clinically relevant improvement in itch numeric rating scale score within 36 hours of administering, wherein the clinically relevant improvement in itch numeric rating scale score is a reduction of 4 or more points in the itch numeric rating scale score compared to baseline, and wherein the patient has a baseline numeric rating scale score of 4 or more.

[0625] 254. The method of embodiment 237, wherein said administration is maintained for at least 2, 4, or 8 weeks.

[0626] 255. The method of embodiment 237, wherein the patient is 12 years of age or older.

[0627] 256. The method of embodiment 255, wherein the patient has a body surface area (BSA) (excluding scalp) involved in atopic dermatitis at baseline of 3% to 20%.

[0628] 257. The method of embodiment 256, wherein the patient has an Investigator's Global Assessment score of 2 to 3 at baseline.

[0629] 258. The method of embodiment 257, wherein the patient has been diagnosed with atopic dermatitis for at least 2 years.

[0630] 259. The method of embodiment 258, wherein the patient is diagnosed with atopic dermatitis as defined by the Hanifin and Rajka criteria.

[0631] 260. The method of embodiment 259, wherein the patient has not used a topical treatment for atopic dermatitis other than an emollient within 2 weeks of baseline.

[0632] 261. The method of embodiment 238, wherein the cream formulation is an oil-in-water emulsion.

[0633] 262. The method of embodiment 261, wherein the cream formulation is a solubilized cream.

[0634] 263. The method of embodiment 262, wherein the cream formulation has a pH of about 2.8 to about 3.6.

[0635] 264. A method of treating atopic dermatitis in a human patient in need thereof, comprising administering twice daily to the skin of the human patient, the cream formulation comprising 0.75% (w / w) ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis, and the patient is Are 12 years of age or older; Investigator's Global Assessment score of 2-3 at baseline Baseline atopic dermatitis involvement between 3% and 20% of the body surface area (excluding scalp); and The method achieving an Investigator's Global Assessment score of 0 or 1 at week 8 of said administration, with at least a 2 point improvement from baseline.

[0636] 265. A method of treating atopic dermatitis in a human patient in need thereof comprising administering twice daily to the skin of the human patient, the cream formulation comprising 0.75% (w / w) ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis, and the patient is Are 12 years of age or older; Investigator's Global Assessment score of 2-3 at baseline Baseline atopic dermatitis involvement between 3% and 20% of the body surface area (excluding scalp); and The method achieving a 75% improvement in Eczema Area and Severity Index score from baseline at week 8 of said administration.

[0637] The present invention will be described in more detail by specific examples. The following examples are provided for illustrative purposes and are not intended to limit the present invention in any manner. Those skilled in the art will easily recognize various non-critical parameters that can be changed or modified to essentially produce the same results. In some embodiments, the present disclosure provides pharmaceutical formulations that include the components specified in the exemplary formulation (e.g., Example 3), where the components are present in the amounts of about Tables 2-5. EXAMPLES

[0638] Example 1: Preparation of an oil-in-water cream formulation of ruxolitinib (INCB018424) phosphate First, to measure the solubility of ruxolitinib (free base) or its 1:1 phosphate salt, approximately 5 mL of potential solvent was added to approximately 50 mg of API or its salt at room temperature. The mixture was suspended and rotated on a wheel. If the mixture became a clear solution, more solid material was added. The suspension was then allowed to slurried for 24 hours. The sample was filtered through a 0.2 micron filter. The liquid portion was collected and diluted with 50 / 50 water-methanol / water. The concentration of the diluted sample was analyzed by HPLC. If the free base or salt was significantly insoluble, the results are only approximate.

[0639] [Table 2] Oil-in-water cream formulations were prepared for the 1:1 ruxolitinib phosphate at 0.5, 1.0, and 1.5% (free base equivalent) by weight of the formulation. The composition of the 15 gram tube is shown in Table 2 below. The formulas for the three strengths were the same, except for adjusting the amount of purified water based on the amount of active ingredient. All excipients used in the formulations were compendial grade (i.e., USP / NF or BP) or approved for use in topical products.

[0640] Quantitative recipes for representative 400 kg batches of 0.5, 1.0, and 1.5% cream formulations are also shown in Tables 3, 4, and 5, respectively.

[0641] Oil-in-water cream formulations were synthesized at 3.5 kg or 400 kg scale according to the following procedure (quantities in Tables 3-5 were appropriately scaled when made at 3.5 kg batch size). Some batches were subject to minor modifications related to scale-up, such as the size of the mixing vessel and mixer. In general, an overhead mixer equipped with high and low shear mixing blades works well for this process.

[0642] procedure The paraben phase was prepared by mixing methylparaben and propylparaben with a portion of the propylene glycol (see % in Tables 2-5).

[0643] 2. Next, the xanthan gum phase was prepared by mixing xanthan gum with propylene glycol (see % in Tables 2-5).

[0644] 3. Next, an oil phase was prepared by mixing light mineral oil, glyceryl stearate, polysorbate 20, white petrolatum, cetyl alcohol, stearyl alcohol, dimethicone, and medium chain triglycerides. This phase was heated to 70-80°C to melt and form a homogenous mixture.

[0645] 4. Next, the aqueous phase was prepared by mixing purified water, polyethylene glycol, and disodium EDTA. This phase was heated to 70-80°C.

[0646] 5. The water phase from Step 4, the paraben phase from Step 1, and Example 2 (Phosphate salt of API) were combined to form a mixture.

[0647] 6. The xanthan gum phase from step 2 was then added to the mixture from step 5.

[0648] 7. The oil phase from step 3 was then combined with the mixture from step 6 under high shear mixing to form an emulsion.

[0649] 8. Phenoxyethanol was then added to the emulsion from step 7. Mixing was continued and the product was then cooled under low shear mixing.

[0650] [Table 3]

[0651] [Table 4]

[0652] [Table 5]

[0653] [Table 6]

[0654] More consistent batches could be obtained at larger scales (e.g., 140 kg) by gradually adding ruxolitinib phosphate to the aqueous phase and then combining with the other phases. Similarly, more consistent batches could be obtained by slower cooling (e.g., by using room temperature water in the reactor jacket rather than cold water).

[0655] Table 5A shows the 0.75% and 1.5% ruxolitinib cream formulations used in Example 3.

[0656] [Table 7]

[0657] Batches were tested for stability at 25°C and found to be stable for up to 24 months at pH consistent with the pH ranges described above (see Tables 7, 9, 11, 12, 13, 15, 17, and 19 of U.S. Patent Publication No. 2015 / 0250790; incorporated herein by reference in their entireties). The viscosity of the cream formulations (e.g., containing 0.75% or 1.5% ruxolitinib phosphate on a free base basis) was ≥17,000 cPs at release and ≥10,000 cPs at shelf life.

[0658] Example 2: A Phase 2, Randomized, Dose-Ranging, Vehicle-Controlled and Triamcinolone 0.1% Cream-Controlled Study to Evaluate the Safety and Efficacy of Topically Applied Ruxolitinib (INCB018424) Phosphate Cream in Adults with Atopic Dermatitis This was a randomized, vehicle- and active (triamcinolone 0.1% cream)-controlled study in subjects with mild to moderate atopic dermatitis (AD). The study was double-blind for vehicle, dose of ruxolitinib cream, and active control. 307 subjects were randomized 1:1:1:1:1:1 to 1.5% ruxolitinib cream BID, 1.5% ruxolitinib cream QD, 0.5% ruxolitinib cream QD, 0.15% ruxolitinib cream QD, vehicle BID, and active control (triamcinolone 0.1% cream BID) and stratified by EASI score (<7 and >7). Ruxolitinib in ruxolitinib cream was expressed as a percentage of ruxolitinib phosphate on a free base basis as % w / w. The ruxolitinib cream formulation was an oil-in-water cream formulation prepared as described in Example 1 (see also U.S. Patent Publication No. 2015 / 0250790), which is incorporated by reference herein in its entirety.

[0659] Subjects receiving the QD regimen applied vehicle at the evening application. Subjects received blinded study medication for 8 weeks. Subjects were randomized to triamcinolone 0.1% cream BID for 4 weeks or vehicle cream for 4 weeks, not to exceed the permitted duration of triamcinolone application.

[0660] Ruxolitinib cream 1.5%, 0.5%, and 0.15% were supplied and applied topically as a thin film to affected areas in the morning and in the evening at least 1 hour before bedtime. Approximately 2 inches (5 cm) of study drug was used for every 1% of BSA (palm with fingers) treated with study drug. Subjects were advised to limit use to no more than one tube per application. If sunscreen, makeup, or other creams were applied to the area to be treated, subjects were instructed to wash the treatment area with mild soap and water and pat dry before applying study drug. If used, topical anti-infectives or other topical treatments were to be avoided for at least 1 hour before or after application of study drug to an area. Subjects were advised to avoid excessive exposure to natural or artificial sunlight (including tanning booths, sunlamps, etc.) and, when outdoors, to wear loose clothing that protects the treatment area from the sun.

[0661] The vehicle cream was identical in appearance to the ruxolitinib cream, except that it contained no active drug. Vehicle cream and triamcinolone 0.1% cream were applied in the same manner as the ruxolitinib cream. Four weeks of triamcinolone 0.1% cream treatment were followed by four weeks of vehicle treatment. Subjects receiving the QD regimen of ruxolitinib cream received vehicle cream during the evening application.

[0662] At week 8, subjects meeting criteria received open-label treatment with 1.5% ruxolitinib cream BID for 4 weeks.

[0663] Subjects who developed additional areas of AD after initiation of treatment were permitted to treat these additional areas (excluding the face and interstitial areas) as long as the total treated BSA did not exceed 20% and there were no safety concerns regarding the additional application of study drug.

[0664] The study population was men or women aged 18–70 years with a diagnosis of atopic dermatitis (AD) for at least 2 years, an Investigator Global Assessment (IGA) score of 2–3, and an involved body surface area (BSA) (excluding face and interstitial areas) of 3% to 20%.

[0665] Subjects could be included in the study if they met all of the following key inclusion criteria: (i) men and women aged 18–70 years, (ii) diagnosed with AD as defined by the Hanifin and Rajka criteria, (iii) had at least a 2-year history of AD, (iv) IGA score of 2–3 at screening and baseline, (v) BSA of AD involvement at screening and baseline excluding face and interstitial areas between 3% and 20%, and (vi) agreed to discontinue all medications used to treat AD from screening to the final follow-up visit.

[0666] Subjects were excluded from the study if they met any of the following major exclusion criteria: (i) evidence of active acute or chronic infection; (ii) use of topical treatment for AD (except mild emollients) within 2 weeks of baseline; (iii) use of systemic immunosuppressants or immunomodulatory drugs (e.g., oral or injectable corticosteroids, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine) within 4 weeks or 5 half-lives (whichever is longer) of baseline; (iv) subjects with other skin diseases other than AD whose presence or treatment may complicate the evaluation of the disease (e.g., psoriasis); (v) history of other diseases other than skin diseases receiving treatment that may complicate the evaluation (e.g., other autoimmune diseases); (vi) white blood cell count <3.0 × 10 at screening. 9(vii) subjects with severe hepatic impairment (Child-Pugh class C) or end-stage renal disease on dialysis or at least one of the following: serum creatinine >1.5 mg / dL, alanine aminotransferase or aspartate aminotransferase ≥1.5 × upper limit of normal; (viii) subjects taking a potent systemic cytochrome P450 3A4 inhibitor or fluconazole within 2 weeks or 5 half-lives, whichever is longer, prior to the Baseline Visit (topical agents with limited systemic availability are allowed); and (ix) subjects who have previously received a systemic or topical Janus kinase inhibitor (e.g., ruxolitinib, tofacitinib, baricitinib, filgotinib, lestaurtinib, or pacritinib).

[0667] The primary endpoint of the study was the percent change from baseline in EASI score at Week 4 in subjects treated with 1.5% ruxolitinib cream BID compared with subjects treated with vehicle cream BID.

[0668] Secondary endpoints were: mean percent change from baseline in EASI score at week 4 for subjects treated with ruxolitinib cream compared to subjects treated with vehicle cream BID; mean percent change from baseline in EASI score at week 4 for subjects treated with ruxolitinib cream compared to subjects treated with triamcinolone 0.1% cream BID; mean percent change from baseline in EASI score at weeks 2 and 8; proportion of subjects achieving ≥ 50% improvement from baseline in EASI (EASI-50) at weeks 2, 4, and 8; These included assessment of dose-response based on percent change from baseline in EASI score at weeks 2, 4, and 8; time to achieve EASI-50; proportion of subjects achieving an IGA score of 0 to 1 with an improvement of ≥2 points from baseline at weeks 2, 4, and 8; mean change from baseline in pruritus Numeric Rating Scale (NRS) score at weeks 2, 4, and 8; safety and tolerability assessed by monitoring the frequency, duration, and severity of adverse events (AEs); performing a physical examination; collecting vital signs; and collecting laboratory data for hematology, serum chemistry, and urinalysis.

[0669] Other secondary outcomes included change from baseline in quality of life based on the Skindex-16 (total, individual questions, and assigned groups) at weeks 2, 4, 8, 10, and 12. The Skindex-16 (Atherton PJ, et al, Support Care Cancer. 2012 Aug;20(8):1729-1735) is a 16-question quality of life assessment that asks subjects how much they were bothered by different aspects of their skin condition in the past week. Patients answered questions about the impact of various AD symptoms in the past week on a scale from 0 (not bothering me) to 6 (always bothering me). Patients were assessed at baseline and at weeks 2, 4, 8, 10, and 12.

[0670] result Patient demographics are shown in Table 6. Baseline clinical characteristics are shown in Table 7. Skindex-16 overall score was 3.7±1.3 at baseline.

[0671] [Table 8]

[0672] [Table 9]

[0673] In the figures showing the triamcinolone results, the triamcinolone (TAC) group received 0.1% triamcinolone cream until week 4, then vehicle.

[0674] Ruxolitinib cream demonstrated significant improvements in EASI scores in a dose- and time-dependent manner across all concentrations compared to vehicle control, as shown in Figure 1. As shown in Figure 2, 1.5% ruxolitinib cream demonstrated the highest efficacy (across all efficacy endpoints) among all treatment groups, with 1.5% ruxolitinib cream BID demonstrating non-inferiority to triamcinolone (TAC) in EASI scores (weeks 2 and 4) and a numerically higher rate of improvement.

[0675] Furthermore, an increasing number of patients achieved EASI-75 (at least 75% improvement in EASI from baseline) in a dose- and time-dependent manner (see Figure 3), with more patients achieving EASI-75 with 1.5% ruxolitinib cream BID at week 4 than with 0.1% TAC.

[0676] As shown in Figure 4, ruxolitinib cream demonstrated significant improvement in IGA response in a dose- and time-dependent manner (IGA responders were patients who achieved an IGA score of 0-1 with a ≥2 point improvement from baseline). Additionally, 1.5% ruxolitinib cream BID demonstrated significantly more IGA responders compared to vehicle at weeks 4 and 8 (Figure 4), with a greater response than 0.1% TAC at week 4.

[0677] As shown in Figure 5, transitioning to 1.5% ruxolitinib cream BID at week 8 resulted in a significant improvement in EASI scores. Similarly, switching to 1.5% ruxolitinib cream BID at week 8 resulted in a substantial improvement in IGA response in all treatment arms (see Figure 6).

[0678] Additionally, as shown in FIG. 7, ruxolitinib cream was associated with a rapid and sustained reduction in itch NRS scores (NRS scores range 0-10, with 0 being no itch and 10 being the worst itch possible). Notably, as shown in FIG. 8 and Table 8, a significant reduction in itch NRS scores was observed with 1.5% ruxolitinib cream BID versus vehicle within 36 hours (i.e., 2 days) of initial application (-1.8 vs. 0.2; p<0.0001). Additionally, transitioning to 1.5% ruxolitinib cream BID at week 8 resulted in a more sustained improvement in itch, as shown in FIG. 9 and Table 8.

[0679] Clinically meaningful reductions in itch NRS scores were observed within 36 hours of initial application of 1.5% ruxolitinib cream BID versus vehicle (-1.8 vs -0.2; P<0.0001). Reductions in itch NRS scores noted within the first 2 weeks of treatment for all ruxolitinib cream regimens were sustained throughout the double-blind period. At week 4, both 1.5% ruxolitinib cream regimens provided more pronounced relief of itch compared with triamcinolone (-50.3) (mean percent change from baseline, -64.6 for 1.5% BID and -54.0 for 1.5% QD). By mean change from baseline, the difference between 1.5% ruxolitinib BID and triamcinolone was statistically significant (-4.0 vs -2.5, respectively; P=0.003). Improvement from baseline in itch NRS scores depended on the treatment regimen, with the mean improvement in patients treated with 1.5% ruxolitinib cream BID at week 8 being 68.5%, significantly better than vehicle (17.6%; P<0.0001).

[0680] Among patients eligible for the CRI analysis (baseline itch NRS ≥ 4, n = 232), a significantly higher proportion of patients receiving ruxolitinib cream achieved a CRI response after only 1 day of treatment than patients receiving vehicle (day 2 response rates for 1.5% ruxolitinib cream BID vs vehicle were 10.5% vs 2.9%), and day 4 response rates for 1.5% ruxolitinib cream BID and vehicle were 26.3% and 2.9, respectively (P < .05). At week 2, significantly more patients achieved CRI with 1.5% ruxolitinib BID (47.5%; P<0.001), 1.5% ruxolitinib QD (32.4%; P<0.01), and 0.5% ruxolitinib QD (25.0%; P<0.05) compared with vehicle (5.4%; Figure 1). Response rates observed with 1.5% ruxolitinib cream BID at week 2 were also significantly higher compared with triamcinolone (19.4%, P<0.05). Cumulative incidence of time to first CRI response was significantly higher in all ruxolitinib cream groups (log-rank P<0.001) compared with vehicle. The median time to first response was shorter in the 1.5% ruxolitinib cream BID and QD treatment groups (8 days and 12.5 days, respectively) compared to vehicle (no response was achieved).

[0681] Similarly, in patients eligible for MCID analysis (baseline itch NRS ≥ 2; n = 272), higher MCID rates were observed as early as day 2 (within 36 hours of treatment initiation) with 1.5% ruxolitinib cream BID (42.5%; P < 0.01) and QD (37.2%; P < 0.05) compared with vehicle (13.6%), and significantly higher MCID rates were also observed with 1.5% ruxolitinib cream BID on day 2 compared with triamcinolone (20.5%; P < 0.05).

[0682] Surprisingly, although baseline itch NRS scores were slightly higher in the dupilumab study (Simpson EL, et al. “Two phase 3 trials of dupilumab versus placebo in atopic dermatitis,” N Engl J Med 2016;375:2335-48), the reduction in itch with ruxolitinib cream in this study appeared greater in an indirect comparison than the improvements reported in patients treated with dupilumab in a phase 3 trial of patients with moderate to severe AD.

[0683] Itch NRS scores and Skindex-16 scores were correlated at baseline. Reduction in itch was positively correlated with reduction in QoL burden (Pearson correlation, 0.67; P < 0.001).

[0684] [Table 10]

[0685] Significant improvements in QoL were observed with all ruxolitinib cream regimens. Improvements were dependent on treatment regimen (Figure 10). The mean percent improvement from baseline in Skindex-16 global score for patients treated with 1.5% ruxolitinib cream BID was 63.5% at week 2 (vehicle, 10.5%; P<0.001) and 73.2% at week 8 (vehicle, 19.7%; P<0.001). At week 4, the mean percent improvement in global score was significantly greater with 1.5% ruxolitinib cream BID (73.7%; P=0.02) compared with triamcinolone (59.7%). Itch NRS scores and Skindex-16 scores were correlated at baseline. Reduction in itch was positively correlated with reduction in QoL burden (Pearson correlation, 0.67; P<0.001).

[0686] As shown in Table 9 (double-blind period), ruxolitinib cream was well tolerated and was not associated with clinically significant site reactions in either the double-blind or open-label periods. There were no serious treatment emergent adverse events (TEAEs) or discontinuations due to TEAEs during the open-label period. All treatment-related adverse events were mild or moderate in severity.

[0687] [Table 11]

[0688] In summary, ruxolitinib cream demonstrated dose- and time-dependent improvements in EASI scores, IGA response, and itch NRS scores. Responses to 1.5% ruxolitinib cream BID during the double-blind period were sustained in the open-label period (week 12: mean 84.9% improvement from baseline in EASI score, 58.5% IGA responders). Patients who crossed over to 1.5% ruxolitinib cream BID during the open-label period experienced greater improvement. The 1.5% ruxolitinib cream BID regimen provided rapid and sustained relief of itch that was significantly greater than triamcinolone at week 4. Finally, ruxolitinib cream was well tolerated, with no serious TEAEs related to study drug and no patients discontinued due to TEAEs.

[0689] Example 3: Two Phase 3, Double-Blind, Randomized, 8-Week, Vehicle-Controlled Efficacy and Safety Studies of Ruxolitinib Cream in Adolescents and Adults with Atopic Dermatitis Followed by a Long-Term Safety Extension Period Two randomized vehicle-controlled (VC) trials were conducted in adolescent and adult participants (≥12 years) with AD who were eligible for topical therapy. Approximately 600 participants in each trial were randomized 2:2:1 to ruxolitinib 0.75% cream BID, ruxolitinib 1.5% cream BID, or vehicle cream. Furthermore, adolescents made up approximately 20% of the total study population. Participants with a baseline IGA score of 2 made up approximately 25% of the total study population. Participants with 3% to 20% BSA of AD involvement and an IGA score of 2 to 3 received 8 weeks of blinded study treatment.

[0690] The ruxolitinib in the cream is present as ruxolitinib phosphate, and the percentages are % (w / w) on a free base basis. The ruxolitinib cream formulation is an oil-in-water cream formulation prepared as described in Example 1 (see Table 5 of U.S. Patent Publication No. 2015 / 0250790; 0.75% ruxolitinib cream was made by adjusting the mass of API in the formulation with water according to the method of Example 1), which is incorporated herein by reference in its entirety.

[0691] Participants who met all study inclusion criteria and none of the exclusion criteria received study drug allocation. The main entry criteria for participants to be eligible for the 8-week VC treatment period were a diagnosis of AD (defined by Hanifin and Rajka criteria) with disease duration of at least 2 years, an IGA score of 2–3, and %BSA involvement (excluding scalp) between 3% and 20% at screening and baseline.

[0692] Participants who developed additional areas of AD were allowed to treat these additional areas with investigator approval, as long as the total treated BSA did not exceed 20% and there were no safety concerns regarding the additional application of study drug. Approval to treat additional areas was to be made by phone during the VC period, although investigators could, at their discretion, ask participants to return for unscheduled visits. Through week 8, participants continued to treat areas identified for treatment at baseline, even if the areas began to improve.

[0693] Efficacy of participants was assessed as the proportion of participants who achieved a treatment response by IGA score at week 8, the primary endpoint of the study. Participants were also assessed for safety and tolerability by monitoring the frequency, duration, and severity of AEs, and physical examinations were performed, and vital signs and clinical / laboratory evaluations were collected at various time points during the study.

[0694] Participants who complete the week 8 assessment without any additional safety concerns will be offered to continue into the long-term safety (LTS) period on the same treatment regimen, except for participants who initially received vehicle, who will be equally assigned to one of the two active treatment arms at week 8. At that point, participants will need an IGA score of 0 to 4 to enter the LTS period. With regard to %BSA, there is no required lower limit; participants may have a BSA ranging from 0% to 20%.

[0695] During the LTS period, participants will attend study visits every 4 weeks until the end of the study (52 weeks in total). At these visits, AD lesions will be assessed by the investigator to determine whether the participant still requires continued treatment (IGA ≥ 1) or can otherwise (re)enter an observation / treatment-free cycle (IGA = 0).

[0696] During the LTS period (i.e., after the week 8 visit), participants will self-assess for AD recurrence and treat areas of skin with active AD changes (not exceeding 20% ​​BSA). If lesions disappear between study visits, participants will stop applying treatment 3 days after lesions disappear. Participants will resume AD treatment at the first sign of recurrence. If new lesions are outside of their usual locations and / or are more widespread than baseline, participants will be required to contact the site for approval.

[0697] Participants will participate in the study for a duration of up to 60 weeks (28 days of screening, 8 weeks of treatment in the VC period, 44 weeks of treatment in the LTS period, and 30(+7) days of safety follow-up).

[0698] The primary endpoint of the study was the proportion of patients achieving the IGA-TS at week 8. Key secondary endpoints of the study were (i) the proportion of participants achieving EASI-75 at week 8, (ii) the proportion of participants achieving a 4-point improvement or greater from baseline in the itch NRS score at week 8, and (iii) the proportion of participants achieving a clinically meaningful improvement in the PROMIS Short Form-Sleep Disorders (8b) 24-hour recall score.

[0699] Other secondary endpoints included: (i) frequency, duration, and severity of adverse events; performance of physical examinations; collection of vital signs; and collection of laboratory data for hematology, serum chemistry, and urinalysis; (ii) proportion of participants achieving IGA-TS at weeks 2 and 4; (iii) proportion of participants achieving an IGA of 0 or 1 at each visit; (iv) proportion of participants achieving ≥4-point improvement in itch NRS score from baseline to weeks 2 and 4; (v) proportion of participants achieving EASI50 at each visit during the VC period; (vi) proportion of participants achieving EASI75 at weeks 2 and 4. (vii) percentage of participants achieving EASI90 at each visit during the VC period; (viii) mean percent change from baseline in EASI score at each visit during the VC period; (ix) mean percent change from baseline in SCORAD score at each visit during the VC period; (x) change from baseline in Itch NRS score at each visit during the VC period; (xi) time to achieve an improvement in Itch NRS score of at least 2, 3, or 4 points; (xii) change from baseline in Skin Pain NRS score at each visit during the VC period; (xiii) change from baseline in Skin Pain NRS score at each visit during the VC period and the proportion of participants who experienced a clinically meaningful improvement in PROMIS Short Form-Sleep Related Disorders (8a) 24-hour recall score at weeks 2, 4, and 8; (xiv) change from baseline in PROMIS Short Form-Sleep Related Disorders (8a) 24-hour recall score and PROMIS Short Form-Sleep Disorders (8b) 24-hour recall score at weeks 2, 4, and 8; (xv) PROMIS Short Form-Sleep Related Disorders (8a) 7-day recall and Short Form-Sleep Disorders (8b) 7-day recall scores at weeks 8, 12, 24, and 52. (xvi) change from baseline in %BSA suffering from AD per visit;(xvii) change from baseline in POEM score at each visit;(xviii) change from baseline in DLQI score at weeks 2, 4, 8, 12, 24, 52, and unscheduled visits;(xix) mean PGIC score at weeks 2, 4, and 8;(xx) percentage of participants with PGIC scores at weeks 2, 4, and 8;(xxi) percentage of participants with PGIC scores of 1 or 2 at weeks 2, 4, and 8;(xxii) change from baseline in EQ-5D-5L score during the VC period;(xxiii) Change from baseline in WPAI-SHP v2.0 at weeks 2, 4, 8, 12, 24, 36, and 52; (xxiv) Trough plasma concentrations of ruxolitinib at all study visits.

[0700] Subjects who met all of the following major inclusion criteria were eligible for inclusion in the study: (i) adolescents aged 12 to 17 years, and men and women aged 18 years or older; (ii) diagnosed with AD as defined by the Hanifin and Rajka criteria; (iii) at least a 2-year history of AD; (iv) an IGA score of 2-3 at screening and baseline during the vehicle-controlled period and an IGA score of 0-4 during the long-term safety period; (v) %BSA of AD involvement excluding scalp is 3% to 20% at screening and baseline during the vehicle-controlled period and %BSA of AD involvement excluding scalp is 0% to 20% during the long-term safety period; (vi) agree to discontinue all medications used to treat AD from screening until the final follow-up visit; (vi) ≥ 10 cm at screening and baseline; 2 (vii) willingness to avoid pregnancy or fathering a child based on the specified criteria; and (viii) ability to understand and willingness to sign an informed consent form, or written informed consent from parent(s) or legal guardian, and written consent from the participant when available.

[0701] Subjects were excluded from the study if they met any of the following major exclusion criteria: (i) participants with an unstable course of AD (spontaneously improving or rapidly worsening) as determined by the investigator in the 4 weeks prior to baseline; (ii) Concomitant symptoms and history of other diseases: (a) immunodeficiency (e.g., lymphoma, acquired immune deficiency syndrome, Wiskott-Aldrich syndrome); (b) chronic or acute infection requiring treatment with systemic antibiotics, antivirals, anthelmintics, antiprotozoals, or antifungals within 2 weeks prior to baseline; (c) active acute bacterial, fungal, or viral skin infection within 1 week prior to baseline (e.g., herpes simplex, shingles, chickenpox); (d) other concomitant skin disorders (e.g., generalized erythroderma such as Netherton syndrome), hyperpigmentation, or extensive scarring) that, in the investigator's opinion, may interfere with the assessment of AD lesions or compromise the participant's safety; (e) AD lesions present only on the hands or feet, without a history of involvement of other early involvement areas such as the face or folds; (f) participants with other types of eczema. (iii) Participant who has a serious illness or medical, physical, or psychiatric condition that, in the opinion of the Investigator, may prevent full participation in the trial, including receiving the investigational product and participating in necessary study visits, may pose a significant risk to the participant, or may interfere with interpretation of the study data. For example, (a) clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months of day 1 of study drug administration, New York Heart Association class III or IV congestive heart failure, and arrhythmias or uncontrolled hypertension (blood pressure >150 / 90 mmHg) requiring treatment, unless approved by the medical monitor / sponsor; (b) participants with a history of malignancy within 5 years prior to enrollment in this study, except for adequately treated non-metastatic malignancies; (c) low hemoglobin (<10 g / dL); (d) severe renal disease on dialysis (serum creatinine >2 mg / dL); (e) current and / or history of liver disease, including known hepatitis B or C with liver or bile duct abnormalities.(iv) Participants who used the following treatments within the indicated washout period prior to baseline: (a) 5 half-lives or 12 weeks, whichever is longer - biologic agents (e.g., dupilumab); (b) 4 weeks - systemic corticosteroids or adrenocorticotropic hormone analogs, cyclosporine, methotrexate, azathioprine, or other systemic immunosuppressants or immunomodulators (e.g., mycophenolate or tacrolimus); (c) 2 weeks - immunizations and sedating antihistamines (non-sedating antihistamines are allowed) unless on a long-term stable regimen; (d) 1 week - use of other topical treatments for AD (excluding mild emollients), such as corticosteroids, calcineurin inhibitors, coal tar (shampoo), antibiotics, or antibacterial cleansing body washes / soaps.Dilute sodium hypochlorite "bleaching" baths are permitted as long as they do not exceed 2 baths per week, with the frequency remaining the same throughout the study;(v) participants who have previously received a systemic or topical JAK inhibitor;(vi) prolonged exposure to ultraviolet light therapy or natural or artificial sources of UV radiation (e.g., sunlight or tanning booths) within 2 weeks prior to baseline, and / or any intention to undergo such exposure during the study that the investigator believes may affect the participant's AD;(vii) positive serological test results screening for HIV antibodies;(viii) liver function tests: AST or ALT ≥ 2 × ULN; alkaline phosphatase and / or bilirubin > 1.5 × ULN (isolated bilirubin > 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin is less than 35%);(ix) pregnant or breastfeeding (x) a history of alcoholism or drug dependence within 1 year prior to screening or current alcohol or drug use that, in the investigator's opinion, would interfere with the participant's ability to comply with the dosing schedule and study assessments; (xi) currently receiving treatment or has been treated within 30 days or 5 half-lives (whichever is longer) prior to baseline with another investigational drug or has current enrollment in another investigational drug protocol; (xii) a participant who, in the investigator's opinion, is unable or unlikely to comply with the dosing schedule and study assessments; (xiii) a participant who is involved with a mental health institution pursuant to an order issued by either a judicial or administrative authority; (xiv) an employee of the Sponsor or the Investigator or otherwise a dependent of either of them.

[0702] The SCORAD is a tool to assess the extent and severity (i.e., intensity) of eczema, completed before, during, and after the start of treatment to determine whether treatment is effective (Oakley, 2009. https: / / www.dermnetnz.org / topics / scorad / . Accessed November 1, 2018.). It was performed during all VC study visits, starting at baseline. To determine extent, the area affected by eczema (A) was calculated as a percentage of the whole body, using the rule of nines or the handprint method. Scores were summed to give a maximum possible value of 100%. To determine intensity, a representative area of ​​eczema was selected (see below for target lesions). The intensity of each of the following signs of redness, swelling, oozing / scabbing, scratching, skin thickening (lichenification), and dryness (which is assessed on areas without inflammation) was rated as none (0), mild (1), moderate (2), or severe (3). The intensity scores were summed to give a "B" (maximum score 18). The subjective symptoms, i.e., itch and insomnia, were scored by participants using a visual analogue scale, where "0" is no itch (or no insomnia) and "10" is the worst itch (or insomnia) possible. These scores were summed to give a "C" (maximum score 20). The total score was calculated by A / 5+7B / 2+C, giving participants a weighting of approximately 60% to intensity and 20% each to extent and subjective symptoms (i.e., insomnia).

[0703] Assessment of target lesions was performed as follows: At baseline, a lesion that was representative of the participant's overall disease and that would be treated with the study drug was selected as the target lesion. This lesion was identified, measured, and recorded in the participant's medical record at each subsequent visit during the VC period. A note had to be made in the participant's medical record, and the location of the target lesion could be marked on a baseline photograph. Target lesions should not be located on the hands, feet, or genitals. Target lesions were selected to be approximately 10 cm in area. 2The longest diameter and measurements perpendicular to the longest diameter were measured in millimeters. After photographs were taken, skin scrapes (using tape discs), lesional skin S. aureus swabs, and TEWL assessments were taken from target lesions before application of study treatment.

[0704] The total %BSA suffered by AD was estimated at each visit during the VC period. Body surface area assessment was guided by the Palmer method, with the palm of the hand holding the five digits together, fingers pressed together, and thumb pressed to the side (handprint) representing 1%BSA, and the thumb representing 0.1%BSA, rounded to the nearest 0.1%.

[0705] A range of patient-reported outcomes were assessed, including quality of life (QoL) using tools such as the Dermatology Life Quality Index (DQLI), Patient Global Impression of Change (PGIC), Patient-Oriented Eczema Measure (POEM), EQ-5D-5L (EQ-5D is a validated self-administered generic utility questionnaire in which participants rate their current health status based on criteria such as mobility, self-care, usual activities, pain / discomfort, and anxiety / depression), the Work Productivity and Activity Impairment Questionnaire: Specific Health Problems version 2.0 (WPAI:SHP), Itch NRS, Skin Pain NRS (Skin Pain Numeric Rating Scale), PROMIS Short Form-Sleep Related Disorders (8a), and PROMIS Short Form-Sleep Disorders (8b). To avoid bias in participant responses to the questionnaires, all of these assessments were completed before any other assessments or study procedures on the day of the study visit and before any discussion with the investigator or study site staff.All patient-reported outcomes were completed at the baseline visit and before the participant's first dose of study medication.

[0706] Participants were given a paper questionnaire or a mobile device (eDiary) for daily assessments. Participants were instructed to complete the diary at specific time points required for each assessment, from the day of screening until week 8 or until cessation of treatment. Daily assessments were performed by participants via the diary starting from the screening visit and all visits during the VC period. Participants assessed (in the past 24 hours): Itch NRS-recording worst level of itch in the evening; Skin Pain NRS-recording worst level of pain in the evening; PROMIS questionnaire; completing the Short Form-Sleep Related Disorders (8a) in the evening; and the Short Form-Sleep Disorders (8b) in the morning.

[0707] During all VC site visits, the following were assessed: EQ-5D-5L - starting at screening; WPAI:SHP - starting at screening; DLQI / CDLQI - starting at day 1; POEM - starting at day 1; PGIC - starting at week 2.

[0708] During the LTS period, EQ-5D-5L; WPAI:SHP; DLQI / CDLQI; POEM; PROMIS Short Form-Sleep Related Disorders (8a) and Short Form-Sleep Disorders (8b) will be assessed.

[0709] The DLQI is a simple, 10-question validated questionnaire to measure how much skin problems have affected participants in the past 7 days, as outlined in the SoAs (Finlay AY, Khan GK, “Dermatology Life Quality Index (DLQI)-a simple practical measure for routine clinical use,” Clin Exp Dermatol 1994;19:210-216.). Participants aged 16 years and older answered the questionnaire as either (1) very much, (2) a lot, (3) a little, or (4) not at all. The questionnaire was analyzed under six headings: symptoms and feelings (questions 1 and 2), daily activities (questions 3 and 4), leisure (questions 5 and 6), work and school (question 7), personal relationships (questions 8 and 9), and treatment (question 10).

[0710] The CDLQI is an adolescent / child version of the DLQI and was completed by adolescents aged 12 years and over and under 16 years. It is self-explanatory and can be easily given to participants. Here, participants are asked to fill it out and can ask for the help of a parent or guardian. The questionnaire was analysed under six headings: symptoms and emotions (questions 1 and 2), leisure (questions 4, 5, and 6), school or holidays (question 7), personal relationships (questions 3 and 8), sleep (question 9), and treatment (question 10).

[0711] Patient's Global Impression of Change The PGIC is a participant self-report measure that reflects the participant's belief about the effectiveness of treatment. The PGIC is a 7-point scale that represents the participant's assessment of their overall improvement and is obtained during site visits during the VC period (Hurst H, Bolton J. “Assessing the clinical significance of change scores recorded on subjective outcome measures,” J Manipulative Physiol Ther 2004;27:26-35). Participants respond as follows: “Since the start of the treatment you received in this study, the atopic dermatitis in the areas treated with the investigational drug has (1) been very improved, (2) been much improved, (3) been minimally improved, (4) been unchanged, (5) been minimally worsened, (6) been much worsened, or (7) been very worse.”

[0712] The POEM is a seven-question quality of life assessment that asks participants how many days in the past seven days they were bothered by different aspects of their skin condition, as outlined in the SoAs (Charman CR, et al., Arch Dermatol 2004,140:1513-1519).

[0713] EQ-5D-5L: The EQ-5D is a validated, self-administered, general utility questionnaire in which participants (adolescents and adults) rate their current health status based on the following criteria (dimensions): mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. 5L indicates that there are five levels of each dimension: no problems, minor problems, moderate problems, major problems, and extreme problems. During all VC period study visits (starting with screening) and certain LTS visits (weeks 12, 24, 36, 52, and follow-up visits), participants were asked to indicate their health status over the past 7 days by checking a box next to the most appropriate statement in each of the five dimensions. The five dimensions can be combined into a five-digit number that represents the participant's health status (EuroQol Research Foundation. EQ-5D-5L. 2017. https: / / euroqol.org / eq-5d-instruments / eq-5d-5l-about / . Accessed July 17, 2018).

[0714] The WPAI:SHP v2.0 questionnaire is a validated 6-item instrument that measures the impact of overall health and specific symptoms on productivity at work and other regular activities over the past 7 days and is completed at all site visits beginning with screening, during the VC period, and at certain LTS visits (12, 24, 36, 52 weeks and follow-up visits) (Reilly MC, Zbrozek AS, Dukes EM, “The validity and reproducibility of a work productivity and activity impairment instrument,” PharmacoEconomics 1993;4:353-365).

[0715] The Itch NRS is a daily patient-reported scale (24-h recall) that measures the worst level of itch intensity. Participants are asked to rate the severity of their itch due to AD by selecting a number from 0 (no itch) to 10 (worst itch imaginable) that best represents the worst level of itch in the past 24 hours. Participants were given a diary to record their itch severity. Participants were instructed to complete the diary every night from the day of screening until their last application of study drug during the VC period.

[0716] The Skin Pain NRS is a daily patient-reported scale (24-h recall) that measures the worst level of pain intensity ranging from 0 (no pain) to 10 (worst pain imaginable). Participants were asked, as outlined in the SoA, "Rate the severity of pain due to your atopic dermatitis skin changes by selecting the number that best represents your worst level of pain over the past 24 hours."

[0717] Participants were given a diary to record the severity of their skin pain each night and to rate their worst pain in the previous 24 hours. Participants were instructed to complete the diary each night from the day of screening until their last application of study drug during the VC period.

[0718] PROMIS® (Patient-Reported Outcomes Measurement Information System) is a set of widely used and accepted patient-reported outcome measures developed and psychometrically supported with robust clinical outcome assessment development methods. Selected PROMIS Short-Form-Sleep-Related Disorders (8a) and Short-Form-Sleep Disorders (8b) questionnaires were adapted to be completed in a daily diary with 24-h recall. The Short-Form-Sleep-Related Disorders (8a) will be collected in the evening and the Short-Form-Sleep Disorders (8b) will be collected in the morning during the VC period. Starting at week 8 and during the LTS period, these will be completed at the sites during the study visit with a 7-day recall period.

[0719] The PROMIS Short Form-Sleep-Related Disorders (8a) questionnaire was completed in the evening during the VC period. This assessment focuses on self-reported perceptions of alertness, sleepiness, and fatigue during normal waking hours and on perceived functional impairments during wakefulness related to sleep or wakefulness disorders (Buysse,Sleep 2010;33:781-792). The questionnaire contains eight brief questions rated on a 5-point scale with scores ranging from 8 to 40, with higher scores indicating greater severity of sleep-related disorders. Each item asks the participant to rate the severity of the participant's sleep disorder. The recall period was the past 24 hours during the VC period and the past 7 days during the LTS period.

[0720] The PROMIS Short Form-Sleep Disturbances (8b) questionnaire was completed in the morning during the VC period. This assessment is a self-reported perception of sleep quality, sleep depth, and sleep-related restoration. Sleep Disturbances does not focus on specific sleep disorder symptoms and does not provide subjective estimates of sleep quantity (e.g., total amount of sleep, time to fall asleep, amount of wakefulness during sleep; Buysse et al., 2010). The Short Form of Sleep Disturbances is general, not disease-specific. The questionnaire is also rated on a 5-point scale with scores ranging from 8 to 40, with higher scores indicating greater severity of sleep disturbance. Each item asked participants to rate the severity of the participant's sleep disturbance. The recall period was the past 24 hours in the VC period and the past 7 days in the LTS period.

[0721] Results of the VC period In TRuE-AD1 (Study 303), 631 patients were randomized (vehicle, n=126; 0.75% BID, n=252; 1.5% BID, n=253). Median (range) age was 32.0 (12-85) years, and 62.0% of patients were female. 73 patients (11.6%) discontinued. In TRuE-AD2 (Study 304), 618 patients were randomized (vehicle, n=124; 0.75% BID, n=248; 1.5% BID, n=246). Median (range) age was 33.0 (12-85) years, and 61.5% were female. 57 patients (9.2%) discontinued. Complete demographics for TRuE-AD1 and TRuE-AD2 are shown in Tables 10 and 11, respectively. Mean baseline itch NRS scores for the pooled TRuE-AD1 and TRuE-AD2 populations of vehicle, 0.75% BID, and 1.5% BID populations were 5.15, 5.14, and 5.09, respectively.

[0722] [Table 12]

[0723] [Table 13]

[0724] The efficacy population consisted of 631 patients in TRuE-AD1 (all randomized) and 577 patients in TRuE-AD2 (vehicle, n=118; 0.75% BID, n=231; 1.5% BID, n=228). All patients who received at least one treatment (all randomized) were included in the safety populations in both studies.

[0725] A summary of the primary and key secondary efficacy endpoints for TRuE-AD1 (Study 303) and TRuE-AD2 (Study 304) are shown in Tables 12 and 13.

[0726] [Table 14]

[0727] [Table 15]

[0728] In TRuE-AD1 and TRuE-AD2, respectively, significantly more patients treated with ruxolitinib cream achieved successful IGA treatment (0.75% BID, 50.0% and 39.0%; 1.5% BID, 53.8% and 51.3%) compared with vehicle (15.1% and 7.6%; all P<0.0001) (Figure 11).

[0729] EASI-75 was achieved by 56.0% and 51.5% of patients who applied ruxolitinib cream 0.75% BID, and 62.1% and 61.8% of patients who applied 1.5% BID, compared with 24.6% and 14.4% of those who applied vehicle (all P<0.0001) in TRuE-AD1 and TRuE-AD2, respectively (Figure 12). In TRuE-AD1 (Study 303), Eczema Area and Severity Index scores decreased over time, with both active treatment groups clearly separated from the vehicle treatment group by week 2. In the pooled TRuE-AD1 (Study 303) and TRuE-AD2 (Study 304) studies, Eczema Area and Severity Index scores decreased over time, with both active treatment groups clearly separated from the vehicle treatment group by week 2 (see Figures 31, 32, and 33).

[0730] In both studies, patients who applied ruxolitinib cream (0.75% BID or 1.5% BID) achieved statistically significant reduction in itch (NRS4) compared to vehicle at week 8 (Figure 13; numbers are for patients with a baseline itch NRS score of 4 or higher). In addition to achieving sustained relief of itch at week 8, patients who applied ruxolitinib cream (0.75% BID or 1.5% BID) also experienced rapid relief of itch within 1-2 days (Figures 14 and 15; Table 14 (TRuE-AD1; mean baseline Itch NRS scores for vehicle, 0.75% BID, and 1.5% BID were 6.39, 6.44, and 6.45, respectively); Table 15 (TRuE-AD2; mean baseline Itch NRS scores for vehicle, 0.75% BID, and 1.5% BID were 6.42, 6.38, and 6.38, respectively); values ​​are for patients with a baseline Itch NRS score of 4 or greater).

[0731] [Table 16]

[0732] [Table 17]

[0733] In both TRuE-AD1 and TRuE-AD2, patients receiving 1.5% ruxolitinib cream BID observed significantly greater itch relief compared to vehicle by day 2 (within 12 hours of first application of ruxolitinib cream) (Table 16 (TRuE-AD1) and Table 17 (TRuE-AD2), measured across patient populations). The mean baseline itch NRS scores for vehicle, 0.75% BID, and 1.5% BID in Table 16 were 5.06, 5.13, and 5.15, respectively. The mean baseline itch NRS scores for vehicle, 0.75% BID, and 1.5% BID in Table 17 were 5.25, 5.15, and 5.02, respectively. By day 2 (within 36 hours of first application of ruxolitinib cream), patients experienced significant relief of pruritus with 0.75% BID ruxolitinib cream in both studies.

[0734] [Table 18]

[0735] [Table 19]

[0736] Pooled data from the TRuE-AD1 and TRuE-AD2 studies for the mean change from baseline in daily itch NRS scores are shown in Table 18 and Figure 25. The p-values ​​indicate that the difference between 0.75% and 1.5% ruxolitinib cream becomes significant by Day 1 (within 12 hours). The mean change from baseline in daily itch NRS scores on Day 1 (within 12 hours) for 0.75% and 1.5% ruxolitinib cream is -0.38 and -0.48, respectively. The mean change from baseline in daily itch NRS scores on Day 2 (within 36 hours) for 0.75% and 1.5% ruxolitinib cream is -1.12 and -1.24, respectively.

[0737] [Table 20]

[0738] In patients with a baseline Itch NRS score of 2 or greater, the number of responders who achieved an improvement in Itch NRS score of 2 or greater by Day 2 (within 36 hours of the first dose of ruxolitinib cream) in patients receiving 0.75% and 1.5% BID ruxolitinib cream reached statistical significance (Table 19 (TRuE-AD1) and Table 20 (TRuE-AD2)).

[0739] [Table 21]

[0740] [Table 22]

[0741] In patients with a baseline Itch NRS score of 2 or greater, the number of responders who achieved an improvement in Itch NRS score of 2 or greater by Day 2 (within 36 hours of the first dose of ruxolitinib cream) in patients receiving 0.75% and 1.5% BID ruxolitinib cream reached statistical significance (Table 21 (TRuE-AD1 and TRuE-AD2)). The difference between 0.75%, 1.5% ruxolitinib cream and vehicle reached statistical significance on Day 1 (within 12 hours).

[0742] [Table 23]

[0743] In patients with a baseline Itch NRS score of 4 or greater, the number of responders who achieved an improvement in Itch NRS score of 4 or greater by day 4 from the first application of ruxolitinib cream for patients receiving 0.75% BID ruxolitinib cream and by day 3 from the first application of ruxolitinib cream for patients receiving 1.5% BID ruxolitinib cream reached statistical significance (Table 22 (TRuE-AD1 and TRuE-AD2 and Figure 26)).

[0744] [Table 24]

[0745] In the TRuE-AD1 study, patients receiving 0.75% and 1.5% BID ruxolitinib cream achieved an IGA score of 0 or 1 by week 2 (Table 23). In the TRuE-AD2 study, patients receiving 1.5% BID ruxolitinib cream achieved an IGA score of 0 or 1 by week 2 and in patients receiving 0.75% BID ruxolitinib cream achieved an IGA score of 0 or 1 by week 4 (Table 24).

[0746] [Table 25]

[0747] [Table 26]

[0748] In patients receiving 0.75% and 1.5% BID ruxolitinib cream, patients achieve EASI90 (Table 25 (TRuE-AD1) and Table 26 (TRuE-AD2)). The difference between 0.75%, 1.5% ruxolitinib cream and vehicle was statistically significant at week 2.

[0749] [Table 27]

[0750] [Table 28]

[0751] At week 8, 21.0% and 20.7% of patients who applied ruxolitinib cream 0.75% BID and 22.3% and 25.6% of patients who applied ruxolitinib cream 1.5% BID in TRuE-AD1 and TRuE-AD2, respectively, achieved a 6-point or greater improvement in the PROMIS sleep disorder score (8a) (Figure 16). At week 8, 21.0% of patients who applied ruxolitinib cream 0.75% BID and 22.3% of patients who applied ruxolitinib cream 1.5% BID in pooled TRuE-AD1 (Study 303) and TRuE-AD2 achieved a 6-point or greater improvement in the PROMIS sleep disorder score (8a) (Figure 30). At week 8, 20.2% and 20.0% of patients who applied ruxolitinib cream 0.75% BID and 21.6% and 23.1% of patients who applied ruxolitinib cream 1.5% BID in TRuE-AD1 and TRuE-AD2, respectively, achieved a 6-point or greater improvement in the PROMIS sleep disorder score (8a) (Figure 17). At week 8, 20.9% of patients who applied ruxolitinib cream 0.75% BID and 23.8% of patients who applied ruxolitinib cream 1.5% BID in pooled TRuE-AD1 (Study 303) and TRuE-AD2 (Study 304) achieved a 6-point or greater improvement in the PROMIS sleep disorder score (8a) (Figure 29).

[0752] For 0.75% BID ruxolitinib cream, IGA-TS and EASI75 patient responses were unexpectedly improved at weeks 2, 4, and 8 compared to 1.5% QD ruxolitinib cream (from Phase 2) (see Tables 27 and 28).

[0753] [Table 29]

[0754] [Table 30]

[0755] The overall rates of treatment-emergent adverse events in both studies after 8 weeks of treatment were comparable between the ruxolitinib cream regimens and vehicle (0.75% BID, 29.4%; 1.5% BID, 28.9%; vehicle, 34.9% in TRuE-AD1; 0.75% BID, 29.4%; 1.5% BID, 23.6%; vehicle, 32.3% in TRuE-AD2). The incidence of serious adverse events was comparable across all treatment groups (0.75% BID, 0.8%; 1.5% BID, 0.6%; vehicle, 0.8%). No clinically significant application site reactions were observed, including in areas of sensitive skin. For example, application site burning occurred at rates equal to or lower than vehicle (0.75% BID, 0.0%; 1.5% BID, 0.8%; Vehicle, 1.6% for TRuE-AD1; 0.75% BID, 0.8%; 1.5% BID, 0.8%; Vehicle, 6.5% for TRuE-AD2). Application site pruritus occurred at rates equal to or lower than vehicle (0.75% BID, 1.2%; 1.5% BID, 0.0%; Vehicle, 1.6%). Hemoglobin (g / L) and platelets (10 9 The changes in serum creatinine (mg / L) were comparable between treatment groups (0.75% BID and 1.5% BID) and vehicle (Figures 18-21).

[0756] Patients with more severe atopic dermatitis and greater body surface involvement Surprisingly, the TRuE-AD1 and TRuE-AD2 studies found that patients with more severe atopic dermatitis and greater body surface involvement appeared to respond well to topical ruxolitinib cream: these patients generally had ≥10% body surface area involved by atopic dermatitis at baseline and a baseline Eczema Area and Severity Index score of ≥16.

[0757] Analyses were performed for TRuE-AD1 and TRuE-AD2 patients with baseline atopic dermatitis-involved body surface area ≥10% and baseline Eczema Area and Severity Index score ≥16. Of the 81 patients in the subgroup, 13 received vehicle, 36 received 0.75% BID ruxolitinib cream, and 32 received 1.5% BID cream. 100% of patients receiving vehicle and 1.5% BID ruxolitinib cream had a baseline IGA score of 3, 33 of 36 patients receiving 0.75% BID ruxolitinib cream had a baseline IGA score of 3, and the remaining patients had a baseline IGA score of 2.

[0758] In both TRuE-AD1 and TRuE-AD2, in patients with ≥10% body surface area involved by atopic dermatitis at baseline and a baseline Eczema Area and Severity Index score ≥16, more patients treated with ruxolitinib cream achieved IGA treatment success compared to vehicle (0.0%) at the vehicle control periods of weeks 2, 4, and 8 (0.75% BID, 30.6%, 38.9%, and 50.0%; 1.5% BID, 25.0%, 46.9%, and 59.4%) (Figure 22).

[0759] In both TRuE-AD1 and TRuE-AD2, more patients treated with ruxolitinib cream achieved IGA treatment success (0.75% BID, 19.9%, 39.1%, and 44.7%; 1.5% BID, 26.2%, 45.1%, and 52.6%) compared to vehicle (3.7%, 6.1%, and 11.5%) at the vehicle control periods of weeks 2, 4, and 8 (Figure 27).

[0760] In TRuE-AD1, in patients with a baseline IGA score of 3 and ≥10% body surface area involved in atopic dermatitis at baseline, more patients treated with ruxolitinib cream achieved IGA treatment success (0.75% BID, 21.0%, 42.0%, and 53.0%; 1.5% BID, 25.3%, 50.6%, and 60.9%) compared with vehicle (0.0%, 4.8%, and 14.3%) at week 2, 4, and 8 vehicle-control periods.

[0761] In both TRuE-AD1 and TRuE-AD2, in patients with ≥10% body surface area involved by atopic dermatitis at baseline and an Eczema Area and Severity Index score ≥16 at baseline, more patients receiving ruxolitinib cream 0.75% BID (36.1%, 63.9%, 75.0% at weeks 2, 4, and 8, respectively) and ruxolitinib cream 1.5% BID (37.5%, 56.3%, 71.9% at weeks 2, 4, and 8, respectively) achieved EASI-75 compared to vehicle (0%, 7.7%, and 7.7% at weeks 2, 4, and 8, respectively) (Figure 23).

[0762] In both TRuE-AD1 and TRuE-AD2, more patients receiving ruxolitinib cream 0.75% BID (28.0%, 47.0%, 53.8% at weeks 2, 4, and 8, respectively) and ruxolitinib cream 1.5% BID (33.9%, 54.7%, 62.0% at weeks 2, 4, and 8, respectively) achieved EASI-75 compared to vehicle (4.9%, 12.3%, and 19.7% at weeks 2, 4, and 8, respectively) (Figure 28).

[0763] In both TRuE-AD1 and TRuE-AD2, in patients with ≥10% body surface area involved by atopic dermatitis at baseline, an Eczema Area and Severity Index score ≥16 at baseline, and an Itch Numeric Rating Scale score ≥4 at baseline, more patients receiving ruxolitinib cream 0.75% BID (23.1%, 42.3%, 50% at weeks 2, 4, and 8, respectively) and ruxolitinib cream 1.5% BID (33.3%, 66.7%, 61.1% at weeks 2, 4, and 8, respectively) achieved itch relief (≥4 point improvement in Itch NRS score) compared to vehicle (0%, 27.3%, and 27.3% at weeks 2, 4, and 8, respectively) (Figure 24).

[0764] Surprisingly, these results indicate that patients with more severe atopic dermatitis, with greater involvement of the body surface, appear to respond equally or better to topical ruxolitinib cream 0.75% or 1.5% BID than patients treated with systemic biologic agents such as dupilumab (see comparisons in Table 29 and Figures 22-24). These results are particularly surprising given that responses to ruxolitinib cream were seen as early as 4-8 weeks compared to 16 weeks of dupilumab.

[0765] [Table 31]

[0766] In addition to those described herein, various modifications of the present invention will be apparent to those skilled in the art from the above description. Such modifications are intended to fall within the scope of the appended claims. Each of the references mentioned in this application is incorporated herein by reference in its entirety.

Claims

1. A topical formulation for treating mild to moderate atopic dermatitis in a human patient comprising 0.75 or 1.5% (w / w) ruxolitinib or a pharma- ceutical acceptable salt thereof on a free base basis, The topical formulation comprises: water, oil component, Emulsifier component, Stabilizers, and Solvent composition Including, the topical formulation is administered to the skin of the human patient twice daily; the human patient has a baseline body surface area (BSA) involved in atopic dermatitis of 20% or less; the human patient has an itch numerical rating scale score of 4 or greater at baseline; the human patient achieves at least a 4 point reduction from baseline in itch numerical rating scale score at 2, 4 or 8 weeks of administration. The topical formulation.

2. 2. The topical formulation of claim 1, wherein the atopic dermatitis is moderate atopic dermatitis.

3. 3. The topical formulation of claim 1 or 2, comprising 0.75% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

4. 3. The topical formulation of claim 1 or 2, comprising 1.5% (w / w) ruxolitinib or a pharma- ceutically acceptable salt thereof on a free base basis.

5. 5. The topical formulation of any one of claims 1-4, wherein the human patient achieves an Investigator's Global Assessment of Therapeutic Success (IGA-TS) as a score of 0 (clear) or 1 (almost clear) with an improvement of ≥2 grades from baseline at week 8 of dosing.

6. The topical formulation of any one of claims 1 to 5, wherein administration of the topical formulation is discontinued at least 8 weeks after the human patient's atopic dermatitis has gone into remission.

7. 7. The topical formulation of any one of claims 1 to 6, wherein the human patient achieves at least a 4 point reduction from baseline in Itch Numeric Rating Scale score at week 4 of administration.

8. 8. The topical formulation of any one of claims 1 to 7, wherein the human patient achieves at least a 1 point reduction from baseline in the Itch Numeric Rating Scale score on the first day of administration.

9. 9. The topical formulation of any one of claims 1 to 8, wherein the human patient achieves at least a 1 point reduction from baseline in the Itch Numeric Rating Scale score on the second day of administration.

10. The topical formulation of any one of claims 1 to 9, wherein the human patient is 12 years of age or older.

11. The topical formulation of any one of claims 1 to 10, wherein the human patient has been diagnosed with atopic dermatitis as defined by the Hanifin and Rajka criteria.

12. 3. The topical formulation of claim 1 or 2, wherein the human patient has a history of atopic dermatitis for at least two years.

13. The topical formulation of any one of claims 1 to 12, wherein ruxolitinib or a pharma- ceutically acceptable salt thereof is ruxolitinib phosphate.

14. The topical formulation of any one of claims 1 to 13, wherein the human patient has 10% or more BSA involved in atopic dermatitis at baseline.

15. 15. The topical formulation of claim 14, wherein the human patient has a baseline Eczema Area and Severity Index (EASI) score of 16 or greater.

16. 2. The topical formulation of claim 1, wherein the ruxolitinib or a pharmaceutically acceptable salt thereof is ruxolitinib phosphate, the human patient is 12 years of age or older, and the human patient has a baseline BSA involved in atopic dermatitis of 10% or more.

17. 17. The topical formulation of claim 16, wherein the human patient has a baseline Eczema Area and Severity Index (EASI) score of 16 or greater.

18. The topical formulation of any one of claims 1 to 5, wherein the ruxolitinib or a pharma- ceutically acceptable salt thereof is ruxolitinib phosphate, the human patient is 12 years of age or older, and the human patient has a baseline BSA involved in atopic dermatitis of 10% or more.

19. 20. The topical formulation of claim 18, wherein the human patient has a baseline Eczema Area and Severity Index (EASI) score of 16 or greater.

20. The topical formulation comprises: 35% to 65% water by weight of the topical formulation; an oil component of 10% to 40% by weight of the topical formulation; 1% to 9% by weight of the topical formulation of an emulsifier component; 0.05% to 5% by weight of the topical formulation of a stabilizer; and A solvent component of the topical formulation of 10% to 35% by weight. Including, A topical formulation according to any one of claims 1 to 19.

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