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

Percentage of Participants Achieving EASI-90 Response at 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.

Time frame: Week 16

Percentage of Participants Achieving EASI-90 Response at Weeks 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.

Time frame: Week 2, 8, 12, 20 and 26

Percentage of Participants Achieving >= 75% Improvement From Baseline in EASI (EASI-75) Response at Weeks 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.

Time frame: Week 2, 4, 8, 12, 16, 20 and 26

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

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

Percentage of Participants Achieving PP-NRS4 From Baseline at Days 2 to 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.

Time frame: Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15

Percentage of Participants Achieving PP-NRS4 From Baseline at 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.

Time frame: Week 4, 8, 12, 16, 20 and 26

Time to Achieve >=4 Points Improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4)

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

Percent Change From Baseline in the Percentage (%) Body Surface Area (BSA) Affected at 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.

Time frame: Baseline (Day 1), Week 2, 4, 8, 12, 16, 20 and 26

Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Total Score at 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.

Time frame: Baseline (Day 1), Week 2, 4, 8, 12, 16, 20 and 26

Change From Baseline in Total Anxiety Score Measured Using the Hospital Anxiety and Depression Scale (HADS) at 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.

Time frame: Baseline (Day 1), Week 12, 16 and 26

Change From Baseline in Total Depression Score Measured Using the HADS at 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.

Time frame: Baseline (Day 1), Week 12, 16 and 26

Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at 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.

Time frame: Baseline (Day 1), Week 2, 12, 16, 20 and 26

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

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

Change From Baseline in Patient-Oriented Eczema Measure (POEM) Total Score at 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.

Time frame: Baseline (Day 1), Week 12, 16 and 26

Change From Baseline in Medical Outcomes Study - Sleep Scale (MOS-Sleep Scale) at 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.

Time frame: Baseline (Day 1), Week 12, 16 and 26

Change From Baseline in Skin Pain NRS at 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.

Time frame: Baseline (Day 1), Week 2, 12, 16, 20 and 26

Medicated Topical Background Therapy-free Days

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

Percentage of Participants Achieving >=4 Points Improvement From Baseline in DLQI at 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.

Time frame: Week 2, 12, 16, 20 and 26