Study of Abrocitinib Compared With Dupilumab in Adults With Moderate to Severe Atopic Dermatitis on Background Topical Therapy

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04345367
• Collaborator: (none)
• Enrollment: 727
• Locations: 151
• Arms: 2
• Actual Duration (Months): 13
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, double-dummy, active-controlled, multi-center study to assess the efficacy and safety of abrocitinib 200 mg (2 x 100 mg tablets) administered orally QD compared with dupilumab 300 mg administered by subcutaneous injection every other week (as per label guidelines) in adult participants on background topical therapy, with moderate to severe AD. The treatment duration is 26 weeks. A total of approximately 600 participants will be enrolled from approximately 220 sites globally. Approximately 600 participants will be randomly assigned to study intervention. There are primary efficacy assessments at Week 2 and Week 4, and a key secondary efficacy assessment at Week 16. Efficacy and safety endpoints will be assessed throughout the entire study. Exploratory endpoints related to hand eczema efficacy will be assessed throughout the study.

Condition or Disease	Intervention/Treatment	Phase
Atopic Dermatitis	Drug: Abrocitinib 200 mg; Combination Product: Dupilumab 300 mg	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 727 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A PHASE 3B RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, ACTIVE CONTROLLED MULTI-CENTER STUDY ASSESSING THE EFFICACY AND SAFETY OF ABROCITINIB COMPARED WITH DUPILUMAB IN ADULT PARTICIPANTS ON BACKGROUND TOPICAL THERAPY WITH MODERATE TO SEVERE ATOPIC DERMATITIS
• Actual Study Start Date: Jun 11, 2020
• Actual Primary Completion Date: Jul 13, 2021
• Actual Study Completion Date: Jul 13, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Abrocitinib 200 mg plus placebo injection Abrocitinib 200 mg daily through Week 26, plus placebo injections every other week through Week 24	Drug: Abrocitinib 200 mg; Abrocitinib 200 mg administered as two 100 mg tablets to be taken orally once daily for 26 weeks. Placebo injections will be administered every other week for 24 weeks.
Active Comparator: Dupilumab 300 mg plus placebo tablets Dupilumab 300 mg every other week (2 injections on Day 1) through Week 24, plus placebo tablets daily through Week 26	Combination Product: Dupilumab 300 mg; Dupilumab 300 mg administered as a single subcutaneous injection every other week for 24 weeks (2 injections on day 1). Placebo tablets will be administered daily.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving Greater Than or Equal to (>=) 4 Points Improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) From Baseline at Week 2 [Week 2]

   The severity of itch (pruritus) due to atopic dermatitis (AD) was assessed using the PP-NRS, a validated horizontal NRS. Participants were asked to assess their worst itching due to AD over the past 24 hours on an NRS with scale ranging from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.

2. Percentage of Participants Achieving >= 90% Improvement From Baseline in Eczema Area and Severity Index (EASI-90) Response at Week 4 [Week 4]

   EASI quantifies severity of AD based on severity of lesion clinical signs and percentage (%) of body surface area (BSA) affected. Severity of clinical signs of AD lesions (erythema, induration/papulation, excoriation and lichenification) were scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin)] and lower limbs [including buttocks]) on a 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based on % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, with higher scores indicating greater severity of AD.

Secondary Outcome Measures

1. Percentage of Participants Achieving EASI-90 Response at Week 16 [Week 16]

   EASI quantifies severity of AD based on severity of lesion clinical signs and % of BSA affected. Severity of clinical signs of AD lesions (erythema, induration/papulation, excoriation and lichenification) were scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin)] and lower limbs [including buttocks]) on a 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based on % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, with higher scores indicating greater severity of AD.

2. Percentage of Participants Achieving EASI-90 Response at Weeks 2, 8, 12, 20 and 26 [Week 2, 8, 12, 20 and 26]

   EASI quantifies severity of AD based on severity of lesion clinical signs and % of BSA affected. Severity of clinical signs of AD lesions (erythema, induration/papulation, excoriation and lichenification) were scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin)] and lower limbs [including buttocks]) on a 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based on % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, with higher scores indicating greater severity of AD.

3. Percentage of Participants Achieving >= 75% Improvement From Baseline in EASI (EASI-75) Response at Weeks 2, 4, 8, 12, 16, 20 and 26 [Week 2, 4, 8, 12, 16, 20 and 26]

   EASI quantifies severity of AD based on severity of lesion clinical signs and % of BSA affected. Severity of clinical signs of AD lesions (erythema, induration/papulation, excoriation and lichenification) were scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin)] and lower limbs [including buttocks]) on a 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based on % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, with higher scores indicating greater severity of AD.

4. Percentage of Participants Achieving Investigator's Global Assessment (IGA) Score of 'Clear' or 'Almost Clear' and >=2 Points Improvement From Baseline up to Week 26 [Week 2, 4, 8, 12, 16, 20 and 26]

   IGA assessed severity of AD on a 5 point scale (0 to 4, higher scores indicate more severity). Scores: 0= clear, except any residual discoloration (post-inflammatory hyperpigmentation and/or hypopigmentation); 1= almost clear, AD not fully cleared- light pink residual lesions (except post-inflammatory hyperpigmentation), just perceptible erythema, papulation/induration lichenification, excoriation, and no oozing/crusting; 2= mild AD with light red lesions, slight but definite erythema, papulation/induration, lichenification, excoriation and no oozing/crusting; 3= moderate AD with red lesions, moderate erythema, papulation/induration, lichenification, excoriation and slight oozing/crusting; 4= severe AD with deep dark red lesions, severe erythema, papulation/induration, lichenification, excoriation and moderate to severe oozing/crusting.

5. Percentage of Participants Achieving PP-NRS4 From Baseline at Days 2 to 15 [Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15]

   The severity of itch (pruritus) due to AD was assessed using the PP-NRS, a validated horizontal NRS. Participants were asked to assess their worst itching due to AD over the past 24 hours on an NRS with scale ranging from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.

6. Percentage of Participants Achieving PP-NRS4 From Baseline at Week 4, 8, 12, 16, 20 and 26 [Week 4, 8, 12, 16, 20 and 26]

   The severity of itch (pruritus) due to AD was assessed using the PP-NRS, a validated horizontal NRS. Participants were asked to assess their worst itching due to AD over the past 24 hours on an NRS with scale ranging from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.

7. Time to Achieve >=4 Points Improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) [Baseline (Day 1) up to Week 30]

   The severity of itch (pruritus) due to AD was assessed using the PP-NRS, a validated horizontal NRS. Participants were asked to assess their worst itching due to AD over the past 24 hours on an NRS with scale ranging from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.

8. Percent Change From Baseline in the Percentage (%) Body Surface Area (BSA) Affected at Week 2, 4, 8, 12, 16, 20 and 26 [Baseline (Day 1), Week 2, 4, 8, 12, 16, 20 and 26]

   The extent (%) to which a body region was involved with AD was determined using handprint method. Number of handprints (size of participant's hand with fingers in a closed position) fitting in the affected area of a body region was estimated. Four body regions were evaluated: head and neck, upper limbs, trunk (including axillae and groin/genitals) and lower limbs (including buttocks). Total number of handprints were 10 for head and neck, 20 for upper limbs, 30 for trunk and 40 for lower limbs. Surface area of body region equivalent to 1 handprint: 1 handprint was equal to 10% for head and neck, 5% for upper limbs, 3.33% for trunk and 2.5% for lower limbs. Percent BSA for a body region was calculated as = total number of handprints in a body region * % surface area equivalent to 1 handprint. Overall % BSA for an individual was derived as sum of % BSA across all 4 body regions and ranged from 0 to 100%, with higher values representing greater severity of AD.

9. Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Total Score at Week 2, 4, 8, 12, 16, 20 and 26 [Baseline (Day 1), Week 2, 4, 8, 12, 16, 20 and 26]

   SCORAD is a scoring index for AD which combined extent (A), severity (B) and subjective symptoms (C). For A, a rule of 9 was used to calculate BSA affected by AD as % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; genitals 1%. Score of each body region was added to determine A (range: 0-100). B: severity of each sign (erythema; edema/papulation; oozing/crusting; excoriation; skin thickening; dryness) was assessed as none (0), mild (1), moderate (2), severe (3); severity scores were added to give B (range: 0-18). C: pruritus and sleep loss, each of these 2 were scored by participant/caregiver using visual analog scale (VAS) where, 0=no itch/no sleep loss and 10=worst imaginable itch/sleep loss, higher scores=worse symptoms. Scores for itch and sleep loss were added to give 'C' (range: 0-20). SCORAD total score was calculated as: A/5+7*B/2+C; range (0-103); higher values=worse outcome.

10. Change From Baseline in Total Anxiety Score Measured Using the Hospital Anxiety and Depression Scale (HADS) at Week 12,16 and 26 [Baseline (Day 1), Week 12, 16 and 26]

    HADS was a validated 14-item questionnaire to assess states of anxiety and depression over the past week. HADS consisted of 2 subscales: HADS-Anxiety (HADS-A) scale and HADS-Depression (HADS-D) scale, each of which comprised of 7 items. Each item was rated on a 4-point scale, with scores ranging from 0 to 3, where higher scores indicated more anxiety/depression symptoms. HADS-A assessed state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks). HADS-A total score was calculated as the sum of all 7 items with score ranging from 0 (no presence of anxiety) to 21 (severe feeling of anxiety); higher score indicated greater severity of anxiety.

11. Change From Baseline in Total Depression Score Measured Using the HADS at Week 12,16 and 26 [Baseline (Day 1), Week 12, 16 and 26]

    HADS was a validated 14-item questionnaire to assess states of anxiety and depression over the past week. HADS consisted of 2 subscales: HADS-A scale and HADS-D scale, each of which comprised of 7 items. Each item was rated on a 4-point scale, with scores ranging from 0 to 3, where higher scores indicated more anxiety/depression symptoms. HADS-D assessed the state of lost interest and diminished pleasure response (lowering of hedonic tone). HADS-D: total score was calculated as the sum of all 7 items with score ranging from 0 (no presence of depression) to 21 (severe feeling of depression); higher score indicated greater severity of depression symptoms.

12. Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 2, 12, 16, 20 and 26 [Baseline (Day 1), Week 2, 12, 16, 20 and 26]

    DLQI is a 10-item questionnaire that measured the impact of skin disease. Each question was evaluated on a 4-point scale (range 0 to 3) where, 0 = not at all, 1= a little, 2= a lot, 3= very much, where higher scores indicated more impact on quality of life. Scores from all 10 questions were added up to give DLQI total score, ranging from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of participants.

13. Change From Baseline in EuroQol Quality of Life 5-Dimension 5-Level (EQ-5D-5L) Visual Analog Scale (VAS) Score at Week 12, 16 and 26 [Baseline (Day 1), Week 12, 16 and 26]

    The EQ-5D-5L is a self-reported health status questionnaire that consisted of six questions used to calculate a health utility score. There were two components to the EQ-5D-5L: a five-item health state profile that assessed mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a VAS that measured health state. EQ-5D VAS was used to record participant's rating for his/her current health-related quality of life state on a vertical VAS with scores ranging from 0 to 100, where 0 = worst imaginable health state and 100 = best imaginable health state.

14. Change From Baseline in Patient-Oriented Eczema Measure (POEM) Total Score at Week 12, 16 and 26 [Baseline (Day 1), Week 12, 16 and 26]

    POEM was a 7-item participant reported outcome measure used to assess the impact of AD (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) over the past week. Each item was scored as: no days=0, 1-2 days=1, 3-4 days=2, 5-6 days=3 and every day=4. The item scores were added to provide a total score ranging from 0 to 28, where higher score indicated greater severity.

15. Change From Baseline in Medical Outcomes Study - Sleep Scale (MOS-Sleep Scale) at Week 12, 16 and 26 [Baseline (Day 1), Week 12, 16 and 26]

    The MOS Sleep Scale is a 12-item measure that is segregated into subscales addressing seven sleep domains (i.e. sleep disturbance, snoring, short of breath or headache, adequacy of sleep, somnolence, sleep problems index I and sleep problems index II). An additional single item assessed quantity of sleep. Each of the sleep domains were scored on a range of 0 to 100, and higher scores indicated worse outcomes. The quantity of sleep scores ranged from 0 to 24 (number of hours slept). Change from baseline scores for each individual sleep domain and quantity of sleep are reported in this outcome measure.

16. Change From Baseline in Skin Pain NRS at Week 2, 12, 16, 20 and 26 [Baseline (Day 1), Week 2, 12, 16, 20 and 26]

    The skin pain NRS was a participant reported outcome where participants were asked to rate the "worst skin pain" in the past 24 hours on a 11-point scale from 0=no skin pain to 10=worst skin pain imaginable. Higher scores indicated worse pain.

17. Medicated Topical Background Therapy-free Days [Day 1 up to Week 26]

    Medicated topical background therapy-free days was defined as number of days where a participant maintained a response of EASI-90 or greater without the use of medicated topical background therapy.

18. Percentage of Participants Achieving >=4 Points Improvement From Baseline in DLQI at Week 2, 12, 16, 20 and 26 [Week 2, 12, 16, 20 and 26]

    DLQI was a 10-item questionnaire that measured the impact of skin disease. Each question was evaluated on a 4-point scale (range 0 to 3) where, 0 = not at all, 1= a little, 2= a lot, 3= very much, where higher scores indicated more impact on quality of life. Scores from all 10 questions were added up to give DLQI total score range from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of participants.

Other Outcome Measures

1. Number of Participants With Treatment Emergent Adverse Events (AEs) [From start of study intervention to 28 days post last dose of study intervention (Up to Week 30)]

   An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a treatment-emergent adverse event (TEAE) if the event started on or after the first dosing day until 28 days post last dose of study drug. AEs included both serious and non-serious AEs.

2. Number of Participants With Serious Adverse Events (SAEs) and AEs Leading to Study Discontinuation [From start of study intervention to 28 days post last dose of study intervention (Up to Week 30)]

   An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; a congenital anomaly/birth defect and other important medical events.

3. Number of Participants With Laboratory Abnormalities Meeting Pre-Defined Criteria [From start of study intervention to 28 days post last dose of study intervention (Up to Week 30)]

   The pre-defined criteria for laboratory parameters included: hemoglobin (<9 grams per deciliter or decreases to >=2 below baseline); platelets (<75*10^3 cells per millimeter cube [mm^3]); lymphocytes (<0.5*10^3 cells per mm^3); neutrophils (<1*10^3 cells per mm^3); aspartate aminotransferase and alanine aminotransferase (>3* upper limit of normal).

4. Number of Participants With Clinically Significant Change From Baseline in Vital Signs [From start of study intervention to 28 days post last dose of study intervention (Up to Week 30)]

   Vital signs including temperature, systolic and diastolic blood pressure, and pulse rate were measured in a seated position after 5 minutes rest. Clinically significant change from baseline in vital signs were determined by the investigator.

5. Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Data [From start of study intervention to 28 days post last dose of study intervention (Up to Week 30)]

   A single 12-lead ECG was performed after the participant has rested for at least 10 minutes quietly in the supine position. Clinically significant change from baseline in ECG data was determined by the investigator.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 18 years of age or older

• Diagnosis of chronic atopic dermatitis (AD) for at least 6 months

• Moderate to severe AD (BSA at least 10%, IGA at least 3, EASI at least 16, and PP-NRS severity score at least 4)

• Recent history of inadequate response to treatment with medicated topical therapy for AD, or who have required systemic therapies for control of their disease

Exclusion Criteria:

• Acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation

• Have increased risk of developing venous thromboembolism

• Unwilling to discontinue current AD medications prior to the study or require treatment with prohibited medications during the study

• Prior treatment with systemic JAK inhibitors or IL-4 or IL-13 antagonists including dupilumab, lebrikizumab or tralokinumab

• Other active non-AD inflammatory skin diseases or conditions affecting skin

• Medical history including thrombocytopenia, coagulopathy or platelet dysfunction, malignancies, current or history of certain infections, lymphoproliferative disorders and other medical conditions at the discretion of the investigator

• Pregnant or breastfeeding women, or women of childbearing potential who are unwilling to use contraception

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Total Skin & Beauty Dermatology Center, PC	Birmingham	Alabama	United States	35205
2	Clinical Research Center Of Alabama	Birmingham	Alabama	United States	35209
3	Alliance Dermatology & MOHS Center, PC	Phoenix	Arizona	United States	85032
4	First OC Dermatology	Fountain Valley	California	United States	92708
5	Ark Clinical Research	Long Beach	California	United States	90806
6	Beach Allergy and Asthma Specialty Group, A Medical Corporation	Long Beach	California	United States	90808
7	Wallace Medical Group, Inc	Los Angeles	California	United States	90056
8	Empire Clinical Research	Pomona	California	United States	91767
9	MedDerm Associates	San Diego	California	United States	92103
10	University of California San Diego Dermatology	San Diego	California	United States	92122
11	University Clinical Trials Inc.	San Diego	California	United States	92123
12	Synergy Dermatology	San Francisco	California	United States	94132
13	Wolverine Clinical Trials, Llc	Santa Ana	California	United States	92705
14	Clinical Science Institute	Santa Monica	California	United States	90404
15	Skin Care Research, LLC	Boca Raton	Florida	United States	33486
16	Olympian Clinical Research	Largo	Florida	United States	33770
17	Miami Dermatology & Laser Research, LLC	Miami	Florida	United States	33173
18	Clinical Neuroscience Solutions, Inc.	Orlando	Florida	United States	32801
19	Accel Research Sites - Pure Skin Dermatology & Aesthetics	Orlando	Florida	United States	32819
20	Clinical Research Trials of Florida, Inc.	Tampa	Florida	United States	33607
21	Olympian Clinical Research	Tampa	Florida	United States	33614
22	Integrated Clinical Research	West Palm Beach	Florida	United States	33406
23	One Health Research Clinic	Norcross	Georgia	United States	30093
24	Sneeze, Wheeze & Itch Associates, LLC	Normal	Illinois	United States	61761
25	Dundee Dermatology	West Dundee	Illinois	United States	60118
26	Dawes Fretzin Clinical Research Group, LLC	Indianapolis	Indiana	United States	46250
27	The South Bend Clinic Center for Research	South Bend	Indiana	United States	46617
28	Epiphany Dermatology of Kansas, LLC	Overland Park	Kansas	United States	66215
29	Avant Research Associates, LLC	Crowley	Louisiana	United States	70526
30	MetroBoston Clinical Partners, LLC	Brighton	Massachusetts	United States	02135
31	Onyx Clinical Research	Flint	Michigan	United States	48507
32	Linden Road Imaging Center	Flint	Michigan	United States	48532
33	Hamzavi Dermatology	Fort Gratiot	Michigan	United States	48059
34	Regional Medical Imaging, P.C. ( Local X-Ray)	Royal Oak	Michigan	United States	48067
35	Revival Research Institute, LLC	Troy	Michigan	United States	48084
36	Skin Specialists, PC	Omaha	Nebraska	United States	68144
37	Vivida Dermatology	Las Vegas	Nevada	United States	89148
38	Psoriasis Treatment Center of Central New Jersey	East Windsor	New Jersey	United States	08520
39	Boice-Willis Clinic, PA	Rocky Mount	North Carolina	United States	27804
40	Carolina Research Center, Inc.	Shelby	North Carolina	United States	28150
41	Oregon Medical Research Center	Portland	Oregon	United States	97223
42	Paddington Testing Co, Inc.	Philadelphia	Pennsylvania	United States	19103
43	Health Concepts	Rapid City	South Dakota	United States	57702
44	Clinical Neuroscience Solutions, Inc.	Memphis	Tennessee	United States	38119
45	International Clinical Research - Tennessee LLC	Murfreesboro	Tennessee	United States	37130
46	Center for Clinical Studies, LTD. LLP	Houston	Texas	United States	77004
47	Dermatology Clinical Research Center of San Antonio	San Antonio	Texas	United States	78229
48	Acclaim Dermatology, PLLC	Sugar Land	Texas	United States	77479
49	Jordan Valley Dermatology Center	West Jordan	Utah	United States	84088
50	St George Dermatology and Skin Cancer Centre	Kogarah	New South Wales	Australia	2217
51	Royal North Shore Hospital	St Leonards	New South Wales	Australia	2065
52	Box Hill Hospital	Box Hill	Victoria	Australia	3128
53	Emeritus Research	Camberwell	Victoria	Australia	3124
54	Skin Health Institute Inc.	Carlton	Victoria	Australia	3053
55	Sinclair Dermatology	East Melbourne	Victoria	Australia	3002
56	Melbourne Health Radiology	Pakrville	Victoria	Australia	3050
57	The Royal Melbourne Hospital	Parkville	Victoria	Australia	3050
58	MHAT Dobrich AD	Dobrich		Bulgaria	9300
59	MC Asklepii OOD	Dupnitsa		Bulgaria	2600
60	DCC Alexandrovska EOOD	Sofia		Bulgaria	1431
61	DCC Fokus-5 - Medical Establishment for Outpatient Care EOOD	Sofia		Bulgaria	1463
62	Military Medical Academy MHAT Sofia	Sofia		Bulgaria	1606
63	Dermatology Research Institute	Calgary	Alberta	Canada	T2J7E1
64	Alberta DermaSurgery Centre	Edmonton	Alberta	Canada	T6G1C3
65	CARE Clinic Ltd	Red Deer	Alberta	Canada	T4P-1K4
66	Dr. Chih-ho Hong Medical Inc	Surrey	British Columbia	Canada	V3R 6A7
67	Wiseman Dermatology Research Inc.	Winnipeg	Manitoba	Canada	R3M 3Z4
68	Karma Clinical Trials, Inc.	St. John's	Newfoundland and Labrador	Canada	A1A 4Y3
69	Kingsway Clinical Research	Etobicoke	Ontario	Canada	M8X 1Y9
70	DermEffects	London	Ontario	Canada	N6H 5L5
71	Lynderm Research Inc.	Markham	Ontario	Canada	L3P 1X2
72	DermEdge Research	Mississauga	Ontario	Canada	L5H 1G9
73	North Bay Dermatology Centre	North Bay	Ontario	Canada	P1B 3Z7
74	The Centre for Clinical Trials	Oakville	Ontario	Canada	L6J 7W5
75	Dermatology Ottawa Research Centre	Ottawa	Ontario	Canada	K2C 3N2
76	SKiN Centre for Dermatology	Peterborough	Ontario	Canada	K9J 5K2
77	The Centre for Dermatology	Richmond Hill	Ontario	Canada	L4B 1A5
78	Medicor Research Inc	Sudbury	Ontario	Canada	P3A 1W8
79	Sudbury Skin Clinique	Sudbury	Ontario	Canada	P3C 1X8
80	Toronto Research Centre	Toronto	Ontario	Canada	M3H5Y8
81	Intermed groupe santé	Chicoutimi	Quebec	Canada	G7H 7Y8
82	Centre de Recherche Dermatologique du Quebec metropolitain	Quebec		Canada	G1V 4x7
83	Centre de Recherche Saint-Louis	Quebec		Canada	G1W4R4
84	Medicien	Las Condes, Santiago	Region Metropolitana	Chile	7580150
85	MIRES (M Y F Estudios Clinicos Limitada)	Nunoa, Santiago	Region Metropolitana	Chile	7750495
86	Vida lntegra	Nunoa, Santiago	Region Metropolitana	Chile	7750495
87	Centro Radiologico Plaza Baquedano	Santiago	Region Metropolitana	Chile	7500906
88	Centro Medico SkinMed Limitada	Santiago	Region Metropolitana	Chile	7580206
89	Hospital Clinico Universidad de Chile	Santiago	Region Metropolitana	Chile	8380456
90	Centro Internacional de Estudios Clinicos - CIEC	Santiago	Region Metropolitana	Chile	8420383
91	Clínica Dermacross S.A.	Santiago	Región Metropolitana	Chile	7640881
92	Terveystalo Tampere	Tampere		Finland	33100
93	Mehiläinen Neo	Turku		Finland	20520
94	Turun yliopistollinen keskussairaala	Turku		Finland	20520
95	Fachklinik Bad Bentheim	Bad Bentheim		Germany	48455
96	Klinikum Bielefeld Rosenhöhe	Bielefeld		Germany	33647
97	Klinische Forschung Dresden GmbH	Dresden		Germany	01069
98	IKF Pneumologie GmbH & Co KG	Frankfurt am Main		Germany	60596
99	SRH Wald-Klinikum Gera GmbH	Gera		Germany	07548
100	Studienzentrum Dr. med. Beate Schwarz	Langenau		Germany	89129
101	SIBAmed GmbH	Leipzig		Germany	04103
102	Universitätsklinikum Schleswig-Holstein, Campus Lübeck	Lübeck		Germany	23538
103	Dermatologische Gemeinschaftspraxis Dres. Quist	Mainz		Germany	55128
104	University of Muenster	Muenster		Germany	48149
105	Clinexpert Kft.	Budapest		Hungary	1033
106	Debreceni Egyetem Klinikai Központ	Debrecen		Hungary	4032
107	Trial Pharma Kft.	Kaposvár		Hungary	7400
108	Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ	Szeged		Hungary	6720
109	Fondazione Policlinico Universitario A. Gemelli IRCCS Universita Cattolica del Sacro Cuore	Roma		Italy	00168
110	Korea University Ansan Hospital	Ansan-si	Gyeonggi-do	Korea, Republic of	15355
111	Chonnam National University Hospital	Gwangju		Korea, Republic of	61469
112	The Catholic University of Korea, Incheon St. Mary's Hospital	Incheon		Korea, Republic of	21431
113	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
114	Chung-Ang University Hospital	Seoul		Korea, Republic of	06973
115	Health Centre 4 Ltd. Diagnostics Centre	Riga		Latvia	LV-1003
116	LLC J.Kisis	Riga		Latvia	LV-1003
117	Outpatient Clinic of Ventspils	Ventspils		Latvia	LV-3601
118	NZOZ Specjalistyczny Osrodek Dermatologiczny DERMAL s.c.	Bialystok		Poland	15-453
119	DERMAPOLIS Medical Dermatology Center	Chorzow		Poland	41-500
120	Uniwersyteckie Centrum Kliniczne	Gdansk		Poland	80-214
121	MCBK	Grodzisk Mazowiecki		Poland	05-825
122	Care Clinic Centrum Medyczne	Katowice		Poland	40-568
123	Krakowskie Centrum Medyczne Sp. z o.o.	Krakow		Poland	31-501
124	Centrum Medyczne Promed	Krakow		Poland	31-513
125	Centrum Terapii Wspolczesnej J.M. Jasnorzewska Spolka Komandytowo-Akcyjna	Lodz		Poland	90-242
126	Niepubliczny Zaklad Opieki Zdrowotnej "DERMED" Centrum Medyczne	Lodz		Poland	90-265
127	Dermedic Jacek Zdybski	Ostrowiec Swietokrzyski		Poland	27-400
128	Gabinety Lekarskie Rivermed	Poznan		Poland	61-441
129	Spolka Cywilna Andrzej Krolicki, Tomasz Kochanowski, ,,Laser Clinic"	Szczecin		Poland	70-332
130	Twoja Przychodnia - Szczecinskie Centrum Medyczne	Szczecin		Poland	71-434
131	Medycyna Kliniczna	Warszawa		Poland	00-874
132	MTZ Clinical Research Sp. z o.o.	Warszawa		Poland	02-106
133	Carpe Diem Centrum Medycyny Estetycznej	Warszawa		Poland	02-661
134	EMC Instytut Medyczny S.A. Przychodnia przy ul. Lowieckiej	Wroclaw		Poland	50-220
135	Cityclinic Przychodnia Lekarsko Psychologiczna Matusiak Spółka Partnerska	Wroclaw		Poland	50-566
136	Centrum Medyczne Oporow	Wroclaw		Poland	52-416
137	Kliniczny Oddzial Chorob Wewnetrznych, Dermatologii i Alergologii	Zabrze		Poland	41-800
138	SUMMIT CLINICAL RESEARCH, s.r.o.	Bratislava		Slovakia	831 01
139	SKINKLINIK s.r.o	Bratislava		Slovakia	83103
140	BeneDerma s.r.o.	Bratislava		Slovakia	841 02
141	Derma therapy spol. s.r.o.	Bratislava		Slovakia	851 01
142	Dermatovenerologicka ambulancia	Nove Zamky		Slovakia	940 34
143	SANARE spol.s.r.o.	Svidnik		Slovakia	089 01
144	Hospital Germans Trias i Pujol	Badalona	Barcelona	Spain	08916
145	Hospital Clinic de Barcelona	Barcelona		Spain	08036
146	Hospital Universitario La Paz	Madrid		Spain	28046
147	Centro de Especialidades Mollabao (Area Sanitaria de Pontevedra e O Salnes)	Pontevedra		Spain	36001
148	Hospital de Montecelo	Pontevedra		Spain	36071
149	Taipei Veterans General Hospital	Taipei City	Taiwan (r.o.c)	Taiwan	11217
150	Taipei Medical University-Shuang Ho Hospital	New Taipei City		Taiwan	23561
151	National Taiwan University Hospital	Taipei		Taiwan	100

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

• Study Protocol - Aug 14, 2020
• Statistical Analysis Plan - Jul 21, 2021

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT04345367
• Other Study ID Numbers: B7451050; 2019-004013-13
• First Posted: Apr 14, 2020
• Last Update Posted: Jul 8, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Pfizer: atopic dermatitis; atopic eczema; eczema; JAK; janus kinase
• Additional relevant MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema; Abrocitinib

Study Results

Participant Flow

Recruitment Details	This was a double-blind, double-dummy, active-controlled study in adult participants with moderate to severe atopic dermatitis. The study was conducted across 143 sites in 15 countries.
Pre-assignment Detail	A total of 940 participants were screened, of which 213 were screen failures and were not enrolled. 727 participants were enrolled in the study and assigned to a study intervention.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Period Title: Overall Study
STARTED	362	365
COMPLETED	327	334
NOT COMPLETED	35	31

Baseline Characteristics

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W	Total
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.	Total of all reporting groups
Overall Participants	362	365	727
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	36.6 (14.6)	35.5 (13.3)	36.0 (14.0)
Sex: Female, Male (Count of Participants)
Female	169 46.7%	161 44.1%	330 45.4%
Male	193 53.3%	204 55.9%	397 54.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	30 8.3%	27 7.4%	57 7.8%
Not Hispanic or Latino	331 91.4%	337 92.3%	668 91.9%
Unknown or Not Reported	1 0.3%	1 0.3%	2 0.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.3%	0 0%	1 0.1%
Asian	62 17.1%	83 22.7%	145 19.9%
Native Hawaiian or Other Pacific Islander	1 0.3%	0 0%	1 0.1%
Black or African American	25 6.9%	26 7.1%	51 7%
White	269 74.3%	248 67.9%	517 71.1%
More than one race	0 0%	3 0.8%	3 0.4%
Unknown or Not Reported	4 1.1%	5 1.4%	9 1.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving Greater Than or Equal to (>=) 4 Points Improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) From Baseline at Week 2
Description	The severity of itch (pruritus) due to atopic dermatitis (AD) was assessed using the PP-NRS, a validated horizontal NRS. Participants were asked to assess their worst itching due to AD over the past 24 hours on an NRS with scale ranging from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) comprised of all randomized participants who received at least one dose of study intervention. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	357	364
Number (95% Confidence Interval) [Percentage of participants]	48.2 13.3%	25.5 7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Cochran-Mantel-Haenszel (CMH) method adjusted by baseline disease severity.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	22.6
	Confidence Interval	(2-Sided) 95%; 15.8 to 29.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimate and confidence interval (CI) for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

2. Primary Outcome

Title	Percentage of Participants Achieving >= 90% Improvement From Baseline in Eczema Area and Severity Index (EASI-90) Response at Week 4
Description	EASI quantifies severity of AD based on severity of lesion clinical signs and percentage (%) of body surface area (BSA) affected. Severity of clinical signs of AD lesions (erythema, induration/papulation, excoriation and lichenification) were scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin)] and lower limbs [including buttocks]) on a 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based on % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, with higher scores indicating greater severity of AD.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

FAS comprised of all randomized participants who received at least one dose of study intervention. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	354	364
Number (95% Confidence Interval) [Percentage of participants]	28.5 7.9%	14.6 4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	CMH method adjusted by baseline disease severity.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	14.1
	Confidence Interval	(2-Sided) 95%; 8.2 to 20.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

3. Secondary Outcome

Title	Percentage of Participants Achieving EASI-90 Response at Week 16
Description	EASI quantifies severity of AD based on severity of lesion clinical signs and % of BSA affected. Severity of clinical signs of AD lesions (erythema, induration/papulation, excoriation and lichenification) were scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin)] and lower limbs [including buttocks]) on a 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based on % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, with higher scores indicating greater severity of AD.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

FAS comprised of all randomized participants who received at least one dose of study intervention. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	357	360
Number (95% Confidence Interval) [Percentage of participants]	54.3 15%	41.9 11.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments	CMH method adjusted by baseline disease severity.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	12.5
	Confidence Interval	(2-Sided) 95%; 5.3 to 19.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

4. Secondary Outcome

Title	Percentage of Participants Achieving EASI-90 Response at Weeks 2, 8, 12, 20 and 26
Description	EASI quantifies severity of AD based on severity of lesion clinical signs and % of BSA affected. Severity of clinical signs of AD lesions (erythema, induration/papulation, excoriation and lichenification) were scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin)] and lower limbs [including buttocks]) on a 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based on % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, with higher scores indicating greater severity of AD.
Time Frame	Week 2, 8, 12, 20 and 26

Outcome Measure Data

Analysis Population Description

FAS comprised of all randomized participants who received at least one dose of study intervention. Here, 'Number Analyzed' signifies participants evaluable for the specified time points.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	362	365
Week 2	11.6 3.2%	7.2 2%
Week 8	45.4 12.5%	25.4 7%
Week 12	47.6 13.1%	33.6 9.2%
Week 20	58.4 16.1%	45.7 12.5%
Week 26	54.6 15.1%	47.6 13%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	4.5
	Confidence Interval	(2-Sided) 95%; 0.2 to 8.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 2. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	20.0
	Confidence Interval	(2-Sided) 95%; 13.2 to 26.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 8. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	14.0
	Confidence Interval	(2-Sided) 95%; 6.9 to 21.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 12. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	12.7
	Confidence Interval	(2-Sided) 95%; 5.5 to 20.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 20. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	6.9
	Confidence Interval	(2-Sided) 95%; -0.4 to 14.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 26. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

5. Secondary Outcome

Title	Percentage of Participants Achieving >= 75% Improvement From Baseline in EASI (EASI-75) Response at Weeks 2, 4, 8, 12, 16, 20 and 26
Description	EASI quantifies severity of AD based on severity of lesion clinical signs and % of BSA affected. Severity of clinical signs of AD lesions (erythema, induration/papulation, excoriation and lichenification) were scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin)] and lower limbs [including buttocks]) on a 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based on % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, with higher scores indicating greater severity of AD.
Time Frame	Week 2, 4, 8, 12, 16, 20 and 26

Outcome Measure Data

Analysis Population Description

FAS comprised of all randomized participants who received at least one dose of study intervention. Here, 'Number Analyzed' signifies participants evaluable for the specified time points.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	362	365
Week 2	29.4 8.1%	21.3 5.8%
Week 4	57.6 15.9%	36.8 10.1%
Week 8	71.0 19.6%	52.8 14.5%
Week 12	76.3 21.1%	61.4 16.8%
Week 16	77.3 21.4%	67.8 18.6%
Week 20	76.1 21%	71.1 19.5%
Week 26	73.0 20.2%	72.3 19.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	8.1
	Confidence Interval	(2-Sided) 95%; 1.8 to 14.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 2. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	20.9
	Confidence Interval	(2-Sided) 95%; 13.8 to 28.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 4. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	18.4
	Confidence Interval	(2-Sided) 95%; 11.4 to 25.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 8. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	14.9
	Confidence Interval	(2-Sided) 95%; 8.2 to 21.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 12. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	9.5
	Confidence Interval	(2-Sided) 95%; 3.0 to 16.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 16. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	5.0
	Confidence Interval	(2-Sided) 95%; -1.4 to 11.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 20. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; -5.9 to 7.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 26. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

6. Secondary Outcome

Title	Percentage of Participants Achieving Investigator's Global Assessment (IGA) Score of 'Clear' or 'Almost Clear' and >=2 Points Improvement From Baseline up to Week 26
Description	IGA assessed severity of AD on a 5 point scale (0 to 4, higher scores indicate more severity). Scores: 0= clear, except any residual discoloration (post-inflammatory hyperpigmentation and/or hypopigmentation); 1= almost clear, AD not fully cleared- light pink residual lesions (except post-inflammatory hyperpigmentation), just perceptible erythema, papulation/induration lichenification, excoriation, and no oozing/crusting; 2= mild AD with light red lesions, slight but definite erythema, papulation/induration, lichenification, excoriation and no oozing/crusting; 3= moderate AD with red lesions, moderate erythema, papulation/induration, lichenification, excoriation and slight oozing/crusting; 4= severe AD with deep dark red lesions, severe erythema, papulation/induration, lichenification, excoriation and moderate to severe oozing/crusting.
Time Frame	Week 2, 4, 8, 12, 16, 20 and 26

Outcome Measure Data

Analysis Population Description

FAS comprised of all randomized participants who received at least one dose of study intervention. Here, 'Number Analyzed' signifies participants evaluable for the specified time points.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	362	365
Week 2	14.4 4%	7.2 2%
Week 4	38.0 10.5%	17.6 4.8%
Week 8	50.1 13.8%	30.9 8.5%
Week 12	51.8 14.3%	36.0 9.9%
Week 16	55.3 15.3%	42.5 11.6%
Week 20	60.0 16.6%	50.8 13.9%
Week 26	55.6 15.4%	51.1 14%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	7.3
	Confidence Interval	(2-Sided) 95%; 2.8 to 11.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 2. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	20.6
	Confidence Interval	(2-Sided) 95%; 14.3 to 26.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 4. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	19.5
	Confidence Interval	(2-Sided) 95%; 12.5 to 26.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 8. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	15.8
	Confidence Interval	(2-Sided) 95%; 8.7 to 23.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 12. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	13.0
	Confidence Interval	(2-Sided) 95%; 5.9 to 20.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 16. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	9.2
	Confidence Interval	(2-Sided) 95%; 2.0 to 16.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 20. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	4.5
	Confidence Interval	(2-Sided) 95%; -2.8 to 11.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 26. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

7. Secondary Outcome

Title	Percentage of Participants Achieving PP-NRS4 From Baseline at Days 2 to 15
Description	The severity of itch (pruritus) due to AD was assessed using the PP-NRS, a validated horizontal NRS. Participants were asked to assess their worst itching due to AD over the past 24 hours on an NRS with scale ranging from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Time Frame	Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15

Outcome Measure Data

Analysis Population Description

FAS comprised of all randomized participants who received at least one dose of study intervention. Here, 'Number Analyzed' signifies participants evaluable for the specified time points.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	362	365
Day 2	11.0 3%	3.8 1%
Day 3	15.1 4.2%	8.6 2.4%
Day 4	22.1 6.1%	10.7 2.9%
Day 5	26.4 7.3%	11.9 3.3%
Day 6	28.4 7.8%	15.5 4.2%
Day 7	33.1 9.1%	13.2 3.6%
Day 8	36.3 10%	14.1 3.9%
Day 9	38.5 10.6%	16.9 4.6%
Day 10	40.0 11%	18.7 5.1%
Day 11	40.1 11.1%	20.2 5.5%
Day 12	41.5 11.5%	20.2 5.5%
Day 13	44.0 12.2%	21.5 5.9%
Day 14	45.5 12.6%	23.2 6.4%
Day 15	48.6 13.4%	25.6 7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	7.1
	Confidence Interval	(2-Sided) 95%; 3.1 to 11.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Day 2. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	6.5
	Confidence Interval	(2-Sided) 95%; 1.7 to 11.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Day 3. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	11.4
	Confidence Interval	(2-Sided) 95%; 6.0 to 16.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Day 4. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	14.5
	Confidence Interval	(2-Sided) 95%; 8.8 to 20.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Day 5. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	12.9
	Confidence Interval	(2-Sided) 95%; 6.9 to 19.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Day 6. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	19.9
	Confidence Interval	(2-Sided) 95%; 13.8 to 26.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Day 7. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	22.1
	Confidence Interval	(2-Sided) 95%; 15.9 to 28.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Day 8. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	21.7
	Confidence Interval	(2-Sided) 95%; 15.2 to 28.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Day 9. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of other
	Estimated Value	21.3
	Confidence Interval	(2-Sided) 95%; 14.7 to 27.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Day 10. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	20.0
	Confidence Interval	(2-Sided) 95%; 13.3 to 26.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Day 11. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	21.3
	Confidence Interval	(2-Sided) 95%; 14.6 to 27.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Day 12. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	22.5
	Confidence Interval	(2-Sided) 95%; 15.8 to 29.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Day 13. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	22.4
	Confidence Interval	(2-Sided) 95%; 15.6 to 29.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Day 14. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	22.9
	Confidence Interval	(2-Sided) 95%; 16.0 to 29.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Day 15. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

8. Secondary Outcome

Title	Percentage of Participants Achieving PP-NRS4 From Baseline at Week 4, 8, 12, 16, 20 and 26
Description	The severity of itch (pruritus) due to AD was assessed using the PP-NRS, a validated horizontal NRS. Participants were asked to assess their worst itching due to AD over the past 24 hours on an NRS with scale ranging from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Time Frame	Week 4, 8, 12, 16, 20 and 26

Outcome Measure Data

Analysis Population Description

FAS comprised of all randomized participants who received at least one dose of study intervention. Here, 'Number Analyzed' signifies participants evaluable for the specified time points.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	362	365
Week 4	58.1 16%	40.8 11.2%
Week 8	65.8 18.2%	52.7 14.4%
Week 12	66.0 18.2%	61.5 16.8%
Week 16	67.2 18.6%	63.6 17.4%
Week 20	65.3 18%	63.2 17.3%
Week 26	68.1 18.8%	63.1 17.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	17.3
	Confidence Interval	(2-Sided) 95%; 10.1 to 24.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 4. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	13.0
	Confidence Interval	(2-Sided) 95%; 6.0 to 20.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 8. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	4.4
	Confidence Interval	(2-Sided) 95%; -2.5 to 11.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 12. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	3.6
	Confidence Interval	(2-Sided) 95%; -3.4 to 10.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 16. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 95%; -4.9 to 9.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 20. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	5.0
	Confidence Interval	(2-Sided) 95%; -1.9 to 11.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 26. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

9. Secondary Outcome

Title	Time to Achieve >=4 Points Improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4)
Description	The severity of itch (pruritus) due to AD was assessed using the PP-NRS, a validated horizontal NRS. Participants were asked to assess their worst itching due to AD over the past 24 hours on an NRS with scale ranging from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Time Frame	Baseline (Day 1) up to Week 30

Outcome Measure Data

Analysis Population Description

FAS comprised of all randomized participants who received at least one dose of study intervention. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	313	303
Median (95% Confidence Interval) [Days]	11.0	25.0

10. Secondary Outcome

Title	Percent Change From Baseline in the Percentage (%) Body Surface Area (BSA) Affected at Week 2, 4, 8, 12, 16, 20 and 26
Description	The extent (%) to which a body region was involved with AD was determined using handprint method. Number of handprints (size of participant's hand with fingers in a closed position) fitting in the affected area of a body region was estimated. Four body regions were evaluated: head and neck, upper limbs, trunk (including axillae and groin/genitals) and lower limbs (including buttocks). Total number of handprints were 10 for head and neck, 20 for upper limbs, 30 for trunk and 40 for lower limbs. Surface area of body region equivalent to 1 handprint: 1 handprint was equal to 10% for head and neck, 5% for upper limbs, 3.33% for trunk and 2.5% for lower limbs. Percent BSA for a body region was calculated as = total number of handprints in a body region * % surface area equivalent to 1 handprint. Overall % BSA for an individual was derived as sum of % BSA across all 4 body regions and ranged from 0 to 100%, with higher values representing greater severity of AD.
Time Frame	Baseline (Day 1), Week 2, 4, 8, 12, 16, 20 and 26

Outcome Measure Data

Analysis Population Description

FAS comprised of all randomized participants who received at least one dose of study intervention.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	362	365
Week 2	-42.7	-33.4
Week 4	-62.0	-49.5
Week 8	-74.0	-62.8
Week 12	-78.8	-69.4
Week 16	-80.6	-73.7
Week 20	-82.2	-76.9
Week 26	-82.3	-79.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-9.3
	Confidence Interval	(2-Sided) 95%; -14.0 to -4.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 2. Analysis was performed using Mixed Model Repeated Measure (MMRM) with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-12.5
	Confidence Interval	(2-Sided) 95%; -17.4 to -7.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 4. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-11.1
	Confidence Interval	(2-Sided) 95%; -15.6 to -6.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 8. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-9.4
	Confidence Interval	(2-Sided) 95%; -13.7 to -5.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 12. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-6.9
	Confidence Interval	(2-Sided) 95%; -10.9 to -2.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 16. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-5.3
	Confidence Interval	(2-Sided) 95%; -9.0 to -1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 20. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-3.4
	Confidence Interval	(2-Sided) 95%; -7.1 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 26. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

11. Secondary Outcome

Title	Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Total Score at Week 2, 4, 8, 12, 16, 20 and 26
Description	SCORAD is a scoring index for AD which combined extent (A), severity (B) and subjective symptoms (C). For A, a rule of 9 was used to calculate BSA affected by AD as % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; genitals 1%. Score of each body region was added to determine A (range: 0-100). B: severity of each sign (erythema; edema/papulation; oozing/crusting; excoriation; skin thickening; dryness) was assessed as none (0), mild (1), moderate (2), severe (3); severity scores were added to give B (range: 0-18). C: pruritus and sleep loss, each of these 2 were scored by participant/caregiver using visual analog scale (VAS) where, 0=no itch/no sleep loss and 10=worst imaginable itch/sleep loss, higher scores=worse symptoms. Scores for itch and sleep loss were added to give 'C' (range: 0-20). SCORAD total score was calculated as: A/5+7*B/2+C; range (0-103); higher values=worse outcome.
Time Frame	Baseline (Day 1), Week 2, 4, 8, 12, 16, 20 and 26

Outcome Measure Data

Analysis Population Description

FAS comprised of all randomized participants who received at least one dose of study intervention.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	362	365
Week 2	-44.5	-33.5
Week 4	-59.6	-46.8
Week 8	-65.8	-55.6
Week 12	-67.9	-60.6
Week 16	-70.6	-64.4
Week 20	-71.8	-66.8
Week 26	-71.5	-68.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-11.0
	Confidence Interval	(2-Sided) 95%; -14.5 to -7.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 2. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-12.8
	Confidence Interval	(2-Sided) 95%; -16.0 to -9.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 4. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-10.2
	Confidence Interval	(2-Sided) 95%; -13.6 to -6.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 8. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-7.3
	Confidence Interval	(2-Sided) 95%; -10.5 to -4.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 12. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-6.1
	Confidence Interval	(2-Sided) 95%; -9.3 to -3.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 16. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-4.9
	Confidence Interval	(2-Sided) 95%; -8.2 to -1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 20. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-3.3
	Confidence Interval	(2-Sided) 95%; -6.6 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 26. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

12. Secondary Outcome

Title	Change From Baseline in Total Anxiety Score Measured Using the Hospital Anxiety and Depression Scale (HADS) at Week 12,16 and 26
Description	HADS was a validated 14-item questionnaire to assess states of anxiety and depression over the past week. HADS consisted of 2 subscales: HADS-Anxiety (HADS-A) scale and HADS-Depression (HADS-D) scale, each of which comprised of 7 items. Each item was rated on a 4-point scale, with scores ranging from 0 to 3, where higher scores indicated more anxiety/depression symptoms. HADS-A assessed state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks). HADS-A total score was calculated as the sum of all 7 items with score ranging from 0 (no presence of anxiety) to 21 (severe feeling of anxiety); higher score indicated greater severity of anxiety.
Time Frame	Baseline (Day 1), Week 12, 16 and 26

Outcome Measure Data

Analysis Population Description

FAS comprised of all randomized participants who received at least one dose of study intervention.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	362	365
Week 12	-0.8	-0.8
Week 16	-1.1	-1.2
Week 26	-1.1	-1.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.4 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 12. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.3 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 16. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.3 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 26. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

13. Secondary Outcome

Title	Change From Baseline in Total Depression Score Measured Using the HADS at Week 12,16 and 26
Description	HADS was a validated 14-item questionnaire to assess states of anxiety and depression over the past week. HADS consisted of 2 subscales: HADS-A scale and HADS-D scale, each of which comprised of 7 items. Each item was rated on a 4-point scale, with scores ranging from 0 to 3, where higher scores indicated more anxiety/depression symptoms. HADS-D assessed the state of lost interest and diminished pleasure response (lowering of hedonic tone). HADS-D: total score was calculated as the sum of all 7 items with score ranging from 0 (no presence of depression) to 21 (severe feeling of depression); higher score indicated greater severity of depression symptoms.
Time Frame	Baseline (Day 1), Week 12, 16 and 26

Outcome Measure Data

Analysis Population Description

FAS comprised of all randomized participants who received at least one dose of study intervention.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	362	365
Week 12	-0.7	-0.7
Week 16	-0.8	-0.9
Week 26	-0.8	-1.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.3 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 12. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.2 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 16. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.1 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 26. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

14. Secondary Outcome

Title	Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 2, 12, 16, 20 and 26
Description	DLQI is a 10-item questionnaire that measured the impact of skin disease. Each question was evaluated on a 4-point scale (range 0 to 3) where, 0 = not at all, 1= a little, 2= a lot, 3= very much, where higher scores indicated more impact on quality of life. Scores from all 10 questions were added up to give DLQI total score, ranging from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of participants.
Time Frame	Baseline (Day 1), Week 2, 12, 16, 20 and 26

Outcome Measure Data

Analysis Population Description

FAS comprised of all randomized participants who received at least one dose of study intervention. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	361	363
Week 2	-8.6	-6.7
Week 12	-10.7	-9.7
Week 16	-10.8	-10.0
Week 20	-10.8	-10.1
Week 26	-10.3	-10.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-2.0
	Confidence Interval	(2-Sided) 95%; -2.6 to -1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 2. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -1.6 to -0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 12. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -1.4 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 16. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.2 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 20. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 26. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

15. Secondary Outcome

Title	Change From Baseline in EuroQol Quality of Life 5-Dimension 5-Level (EQ-5D-5L) Visual Analog Scale (VAS) Score at Week 12, 16 and 26
Description	The EQ-5D-5L is a self-reported health status questionnaire that consisted of six questions used to calculate a health utility score. There were two components to the EQ-5D-5L: a five-item health state profile that assessed mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a VAS that measured health state. EQ-5D VAS was used to record participant's rating for his/her current health-related quality of life state on a vertical VAS with scores ranging from 0 to 100, where 0 = worst imaginable health state and 100 = best imaginable health state.
Time Frame	Baseline (Day 1), Week 12, 16 and 26

Outcome Measure Data

Analysis Population Description

FAS comprised of all randomized participants who received at least one dose of study intervention. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	362	364
Week 12	12.370	11.552
Week 16	12.567	10.474
Week 26	13.484	14.300

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.818
	Confidence Interval	(2-Sided) 95%; -1.220 to 2.856
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 12. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	2.093
	Confidence Interval	(2-Sided) 95%; -0.081 to 4.267
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 16. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.816
	Confidence Interval	(2-Sided) 95%; -2.914 to 1.281
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 26. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

16. Secondary Outcome

Title	Change From Baseline in Patient-Oriented Eczema Measure (POEM) Total Score at Week 12, 16 and 26
Description	POEM was a 7-item participant reported outcome measure used to assess the impact of AD (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) over the past week. Each item was scored as: no days=0, 1-2 days=1, 3-4 days=2, 5-6 days=3 and every day=4. The item scores were added to provide a total score ranging from 0 to 28, where higher score indicated greater severity.
Time Frame	Baseline (Day 1), Week 12, 16 and 26

Outcome Measure Data

Analysis Population Description

FAS comprised of all randomized participants who received at least one dose of study intervention.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	362	365
Week 12	-14.2	-12.6
Week 16	-14.2	-12.8
Week 26	-13.8	-13.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -2.5 to -0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 12. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -2.2 to -0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 16. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.3 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 26. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

17. Secondary Outcome

Title	Change From Baseline in Medical Outcomes Study - Sleep Scale (MOS-Sleep Scale) at Week 12, 16 and 26
Description	The MOS Sleep Scale is a 12-item measure that is segregated into subscales addressing seven sleep domains (i.e. sleep disturbance, snoring, short of breath or headache, adequacy of sleep, somnolence, sleep problems index I and sleep problems index II). An additional single item assessed quantity of sleep. Each of the sleep domains were scored on a range of 0 to 100, and higher scores indicated worse outcomes. The quantity of sleep scores ranged from 0 to 24 (number of hours slept). Change from baseline scores for each individual sleep domain and quantity of sleep are reported in this outcome measure.
Time Frame	Baseline (Day 1), Week 12, 16 and 26

Outcome Measure Data

Analysis Population Description

FAS comprised of all randomized participants who received at least one dose of study intervention.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	362	365
Quantity Hours Slept Score: Week 12	0.7	0.5
Quantity Hours Slept Score: Week 16	0.6	0.5
Quantity Hours Slept Score: Week 26	0.5	0.4
Short of Breath or Headache score: Week 12	-0.7	-1.9
Short of Breath or Headache score: Week 16	-1.2	-1.3
Short of Breath or Headache score: Week 26	-2.0	-2.6
Snoring Score: Week 12	-5.3	-3.5
Snoring Score: Week 16	-4.9	-4.0
Snoring Score: Week 26	-3.9	-4.7
Sleep Disturbance Score: Week 12	-20.5	-16.4
Sleep Disturbance Score: Week 16	-21.5	-17.7
Sleep Disturbance Score: Week 26	-21.2	-19.5
Sleep Adequacy Score: Week 12	13.9	12.9
Sleep Adequacy Score: Week 16	15.7	12.7
Sleep Adequacy Score: Week 26	14.0	13.2
Sleep Somnolence Score: Week 12	-7.7	-6.9
Sleep Somnolence Score: Week 16	-9.8	-7.4
Sleep Somnolence Score: Week 26	-9.9	-7.6
Sleep Problems Index I Score: Week 12	-12.1	-10.9
Sleep Problems Index I Score: Week 16	-13.3	-11.0
Sleep Problems Index I Score: Week 26	-12.9	-12.1
Sleep Problems Index II Score: Week 12	-14.4	-12.2
Sleep Problems Index II Score: Week 16	-15.7	-12.8
Sleep Problems Index II Score: Week 26	-15.4	-14.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.1 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Quantity of hours slept: Week 12. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.2 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Quantity of hours slept: Week 16. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.2 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Quantity of hours slept: Week 26. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; -0.9 to 3.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Short of Breath or Headache score: Week 12. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -2.0 to 2.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Short of Breath or Headache score: Week 16. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -1.5 to 2.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Short of Breath or Headache score: Week 26. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-1.8
	Confidence Interval	(2-Sided) 95%; -4.2 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Snoring score: Week 12. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -3.3 to 1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Snoring score: Week 16. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; -1.7 to 3.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Snoring score: Week 26. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-4.1
	Confidence Interval	(2-Sided) 95%; -6.6 to -1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sleep disturbance score: Week 12. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-3.8
	Confidence Interval	(2-Sided) 95%; -6.2 to -1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sleep disturbance score: Week 16. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -4.1 to 0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sleep disturbance score: Week 26. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -1.6 to 3.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sleep adequacy score: Week 12. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	2.9
	Confidence Interval	(2-Sided) 95%; 0.4 to 5.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sleep adequacy score: Week 16. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; -1.9 to 3.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sleep adequacy score: Week 26. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -2.8 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sleep somnolence score: Week 12. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -4.4 to -0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sleep somnolence score: Week 16. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 95%; -4.3 to -0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sleep somnolence score: Week 26. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -3.0 to 0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sleep Problems Index I score: Week 12. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 95%; -4.0 to -0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sleep Problems Index I score: Week 16. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -2.5 to 0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sleep Problems Index I score: Week 26. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-2.2
	Confidence Interval	(2-Sided) 95%; -4.0 to -0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sleep Problems Index II score: Week 12. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-2.9
	Confidence Interval	(2-Sided) 95%; -4.8 to -1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sleep Problems Index II score: Week 16. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -3.2 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sleep Problems Index II score: Week 26. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

18. Secondary Outcome

Title	Change From Baseline in Skin Pain NRS at Week 2, 12, 16, 20 and 26
Description	The skin pain NRS was a participant reported outcome where participants were asked to rate the "worst skin pain" in the past 24 hours on a 11-point scale from 0=no skin pain to 10=worst skin pain imaginable. Higher scores indicated worse pain.
Time Frame	Baseline (Day 1), Week 2, 12, 16, 20 and 26

Outcome Measure Data

Analysis Population Description

FAS comprised of all randomized participants who received at least one dose of study intervention.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	362	365
Week 2	-3.7	-2.6
Week 12	-4.5	-4.0
Week 16	-4.4	-4.2
Week 20	-4.8	-4.5
Week 26	-4.5	-4.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -1.5 to -0.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 2. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -0.8 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 12. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.6 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 16. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.6 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 20. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.5 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 26. Analysis was performed using MMRM with fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, baseline value and an unstructured covariance matrix.

19. Secondary Outcome

Title	Medicated Topical Background Therapy-free Days
Description	Medicated topical background therapy-free days was defined as number of days where a participant maintained a response of EASI-90 or greater without the use of medicated topical background therapy.
Time Frame	Day 1 up to Week 26

Outcome Measure Data

Analysis Population Description

FAS comprised of all randomized participants who received at least one dose of study intervention.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	362	365
Least Squares Mean (95% Confidence Interval) [Days]	51.4	33.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments	Analysis was performed using analysis of covariance (ANCOVA) model including treatment as a main effect and baseline disease severity as covariates.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	18.1
	Confidence Interval	(2-Sided) 95%; 10.5 to 25.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Percentage of Participants Achieving >=4 Points Improvement From Baseline in DLQI at Week 2, 12, 16, 20 and 26
Description	DLQI was a 10-item questionnaire that measured the impact of skin disease. Each question was evaluated on a 4-point scale (range 0 to 3) where, 0 = not at all, 1= a little, 2= a lot, 3= very much, where higher scores indicated more impact on quality of life. Scores from all 10 questions were added up to give DLQI total score range from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of participants.
Time Frame	Week 2, 12, 16, 20 and 26

Outcome Measure Data

Analysis Population Description

FAS comprised of all randomized participants who received at least one dose of study intervention. Here, 'Number Analyzed' signifies participants evaluable for the specified time points.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	362	365
Week 2	81.3 22.5%	67.5 18.5%
Week 12	85.4 23.6%	81.4 22.3%
Week 16	82.7 22.8%	84.2 23.1%
Week 20	81.8 22.6%	83.7 22.9%
Week 26	76.6 21.2%	80.8 22.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	13.7
	Confidence Interval	(2-Sided) 95%; 7.3 to 20.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 2. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	3.9
	Confidence Interval	(2-Sided) 95%; -1.6 to 9.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 12. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -7.1 to 4.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 16. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	-2.0
	Confidence Interval	(2-Sided) 95%; -7.6 to 3.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 20. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Abrocitinib 200 mg QD, Dupilumab 300 mg Q2W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	-4.2
	Confidence Interval	(2-Sided) 95%; -10.3 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 26. The estimate and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions.

21. Other Pre-specified Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (AEs)
Description	An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a treatment-emergent adverse event (TEAE) if the event started on or after the first dosing day until 28 days post last dose of study drug. AEs included both serious and non-serious AEs.
Time Frame	From start of study intervention to 28 days post last dose of study intervention (Up to Week 30)

Outcome Measure Data

Analysis Population Description

Safety population comprised of all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	362	365
Count of Participants [Participants]	268 74%	239 65.5%

22. Other Pre-specified Outcome

Title	Number of Participants With Serious Adverse Events (SAEs) and AEs Leading to Study Discontinuation
Description	An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; a congenital anomaly/birth defect and other important medical events.
Time Frame	From start of study intervention to 28 days post last dose of study intervention (Up to Week 30)

Outcome Measure Data

Analysis Population Description

Safety population comprised of all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	362	365
SAEs	6 1.7%	6 1.6%
AEs Leading to Study Discontinuation	12 3.3%	9 2.5%

23. Other Pre-specified Outcome

Title	Number of Participants With Laboratory Abnormalities Meeting Pre-Defined Criteria
Description	The pre-defined criteria for laboratory parameters included: hemoglobin (<9 grams per deciliter or decreases to >=2 below baseline); platelets (<75*10^3 cells per millimeter cube [mm^3]); lymphocytes (<0.5*10^3 cells per mm^3); neutrophils (<1*10^3 cells per mm^3); aspartate aminotransferase and alanine aminotransferase (>3* upper limit of normal).
Time Frame	From start of study intervention to 28 days post last dose of study intervention (Up to Week 30)

Outcome Measure Data

Analysis Population Description

Safety population comprised of all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	362	365
Count of Participants [Participants]	38 10.5%	10 2.7%

24. Other Pre-specified Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Description	Vital signs including temperature, systolic and diastolic blood pressure, and pulse rate were measured in a seated position after 5 minutes rest. Clinically significant change from baseline in vital signs were determined by the investigator.
Time Frame	From start of study intervention to 28 days post last dose of study intervention (Up to Week 30)

Outcome Measure Data

Analysis Population Description

Safety population comprised of all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	362	365
Count of Participants [Participants]	0 0%	0 0%

25. Other Pre-specified Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Data
Description	A single 12-lead ECG was performed after the participant has rested for at least 10 minutes quietly in the supine position. Clinically significant change from baseline in ECG data was determined by the investigator.
Time Frame	From start of study intervention to 28 days post last dose of study intervention (Up to Week 30)

Outcome Measure Data

Analysis Population Description

Safety population comprised of all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Arm/Group Title	Abrocitinib 200 mg QD	Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.	Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
Measure Participants	362	365
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	From start of study intervention up to 28 days after last dose of study intervention (Up to Week 30)
Adverse Event Reporting Description	An AE term may be reported as both a serious and non-serious AE, but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Arm/Group Title	Abrocitinib 200 mg QD		Dupilumab 300 mg Q2W
Arm/Group Description	Participants were administered abrocitinib 200 mg (2 x 100 mg) oral tablets once daily (QD) from Day 1 to Week 26 along with dupilumab-matching placebo administered as a subcutaneous injection once every 2 weeks (Q2W) until Week 24. Participants were followed for up to 4 weeks post last dose of study intervention.		Participants were administered dupilumab 300 mg as a subcutaneous injection Q2W until Week 24 along with abrocitinib-matching placebo oral tablets administered once daily from Day 1 to Week 26. Participants were followed for up to 4 weeks post last dose of study intervention.
All Cause Mortality
	Abrocitinib 200 mg QD		Dupilumab 300 mg Q2W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/362 (0.6%)		0/365 (0%)
Serious Adverse Events
	Abrocitinib 200 mg QD		Dupilumab 300 mg Q2W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/362 (1.7%)		6/365 (1.6%)
Cardiac disorders
Cardio-respiratory arrest	1/362 (0.3%)		0/365 (0%)
Hepatobiliary disorders
Cholecystitis acute	1/362 (0.3%)		0/365 (0%)
Infections and infestations
COVID-19	1/362 (0.3%)		0/365 (0%)
COVID-19 pneumonia	1/362 (0.3%)		0/365 (0%)
Pneumonia	1/362 (0.3%)		0/365 (0%)
Injury, poisoning and procedural complications
Upper limb fracture	1/362 (0.3%)		0/365 (0%)
Investigations
Alanine aminotransferase increased	0/362 (0%)		1/365 (0.3%)
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	0/362 (0%)		1/365 (0.3%)
Rhabdomyolysis	0/362 (0%)		1/365 (0.3%)
Nervous system disorders
Haemorrhage intracranial	1/362 (0.3%)		0/365 (0%)
Renal and urinary disorders
Nephrotic syndrome	0/362 (0%)		1/365 (0.3%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/362 (0%)		1/365 (0.3%)
Skin and subcutaneous tissue disorders
Dermatitis atopic	0/362 (0%)		1/365 (0.3%)
Other (Not Including Serious) Adverse Events
	Abrocitinib 200 mg QD		Dupilumab 300 mg Q2W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	203/362 (56.1%)		144/365 (39.5%)
Gastrointestinal disorders
Diarrhoea	8/362 (2.2%)		8/365 (2.2%)
Nausea	70/362 (19.3%)		8/365 (2.2%)
Vomiting	11/362 (3%)		6/365 (1.6%)
General disorders
Fatigue	10/362 (2.8%)		5/365 (1.4%)
Infections and infestations
COVID-19	14/362 (3.9%)		12/365 (3.3%)
Conjunctivitis	8/362 (2.2%)		35/365 (9.6%)
Folliculitis	12/362 (3.3%)		3/365 (0.8%)
Herpes simplex	12/362 (3.3%)		5/365 (1.4%)
Herpes zoster	9/362 (2.5%)		2/365 (0.5%)
Nasopharyngitis	14/362 (3.9%)		12/365 (3.3%)
Oral herpes	9/362 (2.5%)		15/365 (4.1%)
Upper respiratory tract infection	10/362 (2.8%)		9/365 (2.5%)
Urinary tract infection	8/362 (2.2%)		7/365 (1.9%)
Investigations
Blood creatine phosphokinase increased	14/362 (3.9%)		13/365 (3.6%)
Natural killer cell count decreased	10/362 (2.8%)		0/365 (0%)
SARS-CoV-2 test positive	15/362 (4.1%)		13/365 (3.6%)
Weight increased	8/362 (2.2%)		3/365 (0.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/362 (0.6%)		8/365 (2.2%)
Nervous system disorders
Dizziness	10/362 (2.8%)		4/365 (1.1%)
Headache	47/362 (13%)		24/365 (6.6%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	8/362 (2.2%)		1/365 (0.3%)
Skin and subcutaneous tissue disorders
Acne	46/362 (12.7%)		10/365 (2.7%)
Dermatitis atopic	17/362 (4.7%)		13/365 (3.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.