Trial Outcomes & Findings for Study of Baricitinib (LY3009104) in Patients With Moderate to Severe Atopic Dermatitis (NCT NCT03334422)

Results Overview

The IGA measures the investigator's global assessment of the participants overall severity of their atopic dermatitis (AD), based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

615 participants

Primary outcome timeframe

16 Weeks

Results posted on

2020-01-22

Participant Flow

Participants who completed double blind treatment phase had option to enter extension study I4V-MC-JAHN (NCT03334435).

Participant milestones

Participant milestones
Measure	Placebo Placebo administered orally once daily.	1mg Baricitinib 1 milligram (mg) Baricitinib administered orally once daily.	2mg Baricitinib 2mg Baricitinib administered orally once daily.	4mg Baricitinib 4mg Baricitinib administered orally once daily.
Overall Study STARTED	244	125	123	123
Overall Study Received at Least One Dose of Study Drug	244	124	123	123
Overall Study COMPLETED	225	115	113	117
Overall Study NOT COMPLETED	19	10	10	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo administered orally once daily.	1mg Baricitinib 1 milligram (mg) Baricitinib administered orally once daily.	2mg Baricitinib 2mg Baricitinib administered orally once daily.	4mg Baricitinib 4mg Baricitinib administered orally once daily.
Overall Study Adverse Event	1	3	2	2
Overall Study Lack of Efficacy	10	2	7	3
Overall Study Withdrawal by Subject	8	3	1	0
Overall Study Lost to Follow-up	0	0	0	1
Overall Study Inability to obtain laboratory samples	0	1	0	0
Overall Study Pregnancy	0	1	0	0

Baseline Characteristics

Study of Baricitinib (LY3009104) in Patients With Moderate to Severe Atopic Dermatitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=244 Participants Placebo administered orally once daily.	1mg Baricitinib n=125 Participants 1 milligram (mg) Baricitinib administered orally once daily.	2mg Baricitinib n=123 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=123 Participants 4mg Baricitinib administered orally once daily.	Total n=615 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	235 Participants n=5 Participants	124 Participants n=7 Participants	118 Participants n=5 Participants	119 Participants n=4 Participants	596 Participants n=21 Participants
Age, Categorical >=65 years	9 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	19 Participants n=21 Participants
Sex: Female, Male Female	90 Participants n=5 Participants	45 Participants n=7 Participants	58 Participants n=5 Participants	41 Participants n=4 Participants	234 Participants n=21 Participants
Sex: Female, Male Male	154 Participants n=5 Participants	80 Participants n=7 Participants	65 Participants n=5 Participants	82 Participants n=4 Participants	381 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	72 Participants n=5 Participants	36 Participants n=7 Participants	37 Participants n=5 Participants	38 Participants n=4 Participants	183 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	169 Participants n=5 Participants	85 Participants n=7 Participants	85 Participants n=5 Participants	82 Participants n=4 Participants	421 Participants n=21 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	10 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment Argentina	28 Participants n=5 Participants	14 Participants n=7 Participants	13 Participants n=5 Participants	12 Participants n=4 Participants	67 Participants n=21 Participants
Region of Enrollment South Korea	24 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants	9 Participants n=4 Participants	55 Participants n=21 Participants
Region of Enrollment Austria	13 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	7 Participants n=4 Participants	31 Participants n=21 Participants
Region of Enrollment Hungary	23 Participants n=5 Participants	10 Participants n=7 Participants	11 Participants n=5 Participants	8 Participants n=4 Participants	52 Participants n=21 Participants
Region of Enrollment Japan	45 Participants n=5 Participants	22 Participants n=7 Participants	22 Participants n=5 Participants	23 Participants n=4 Participants	112 Participants n=21 Participants
Region of Enrollment Poland	41 Participants n=5 Participants	27 Participants n=7 Participants	21 Participants n=5 Participants	29 Participants n=4 Participants	118 Participants n=21 Participants
Region of Enrollment Israel	12 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	9 Participants n=4 Participants	34 Participants n=21 Participants
Region of Enrollment Australia	24 Participants n=5 Participants	14 Participants n=7 Participants	15 Participants n=5 Participants	14 Participants n=4 Participants	67 Participants n=21 Participants
Region of Enrollment Switzerland	13 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	2 Participants n=4 Participants	25 Participants n=21 Participants
Region of Enrollment Spain	21 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants	10 Participants n=4 Participants	54 Participants n=21 Participants

PRIMARY outcome

Timeframe: 16 Weeks

Population: All participants randomized to placebo, 2mg, or 4mg of study drug.

The IGA measures the investigator's global assessment of the participants overall severity of their atopic dermatitis (AD), based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.

Outcome measures

Outcome measures
Measure	Placebo n=244 Participants Placebo administered orally once daily.	2mg Baricitinib n=123 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=123 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib 4mg Baricitinib administered orally once daily.
Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement (Placebo, 2mg and 4mg Baricitinib)	4.5 percentage of participants	10.6 percentage of participants	13.8 percentage of participants	—

SECONDARY outcome

Timeframe: 16 Weeks

Population: All participants randomized to placebo or 1mg of study drug.

The IGA measures the investigator's global assessment of the participants overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.

Outcome measures

Outcome measures
Measure	Placebo n=244 Participants Placebo administered orally once daily.	2mg Baricitinib n=125 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib 4mg Baricitinib administered orally once daily.	4mg Baricitinib 4mg Baricitinib administered orally once daily.
Percentage of Participants Achieving IGA of 0 or 1 With a ≥ 2 Point Improvement (Placebo, 1mg Baricitinib)	4.5 percentage of participants	8.8 percentage of participants	—	—

SECONDARY outcome

Timeframe: 16 Weeks

Population: All randomized participants.

The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2 and 3. The final EASI score is obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score.

Outcome measures

Outcome measures
Measure	Placebo n=244 Participants Placebo administered orally once daily.	2mg Baricitinib n=125 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=123 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=123 Participants 4mg Baricitinib administered orally once daily.
Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75)	6.1 percentage of participants	12.8 percentage of participants	17.9 percentage of participants	21.1 percentage of participants

SECONDARY outcome

Timeframe: 16 Weeks

Population: All randomized participants

The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100%) and the severity of 4 clinical signs (1) erythema, (2)edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2 and 3. The final EASI score is obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI90 is defined as a ≥ 90% improvement from baseline in the EASI score.

Outcome measures

Outcome measures
Measure	Placebo n=244 Participants Placebo administered orally once daily.	2mg Baricitinib n=125 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=123 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=123 Participants 4mg Baricitinib administered orally once daily.
Percentage of Participants Achieving EASI90	2.5 percentage of participants	6.4 percentage of participants	8.9 percentage of participants	13.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 16 Weeks

Population: All randomized participants who had a week 16 EASI data.

The EASI assesses objective physician estimates of 2 dimensions of AD - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs (1) erythema (2)edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2 and 3. The final EASI score is obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). Least Square (LS) Means were calculated using a mixed model repeated measures (MMRM) model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.

Outcome measures

Outcome measures
Measure	Placebo n=52 Participants Placebo administered orally once daily.	2mg Baricitinib n=34 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=40 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=49 Participants 4mg Baricitinib administered orally once daily.
Percent Change From Baseline on EASI Score	-28.91 Percent Change Standard Error 4.32	-41.68 Percent Change Standard Error 5.33	-54.80 Percent Change Standard Error 4.99	-54.88 Percent Change Standard Error 4.56

SECONDARY outcome

Timeframe: 16 Weeks

Population: All randomized participants.

The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable Itching or lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), \& subjective symptoms (C: 0-20) combine using A/5 + 7\*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. The SCORAD75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the SCORAD score.

Outcome measures

Outcome measures
Measure	Placebo n=244 Participants Placebo administered orally once daily.	2mg Baricitinib n=125 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=123 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=123 Participants 4mg Baricitinib administered orally once daily.
Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75)	1.6 percentage of participants	4.8 percentage of participants	7.3 percentage of participants	11.4 percentage of participants

SECONDARY outcome

Timeframe: 16 Weeks

Population: All randomized participants with a baseline Itch NRS score ≥ 4.

The Itch Numeric Rating Scale (NRS) is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participants itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours.

Outcome measures

Outcome measures
Measure	Placebo n=213 Participants Placebo administered orally once daily.	2mg Baricitinib n=100 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=106 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=107 Participants 4mg Baricitinib administered orally once daily.
Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS)	4.7 percentage of participants	6.0 percentage of participants	15.1 percentage of participants	18.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 16 Weeks

Population: All randomized participants with a Week 16 ADSS Item 2 (frequency of waking) data.

Atopic Dermatitis Sleep Scale (ADSS) is a 3-item, participant-administered questionnaire developed to assess the impact of itch on sleep including difficulty falling asleep, frequency of waking, and difficulty getting back to sleep last night. Item 2, frequency of waking last night is reported by selecting the number of times they woke up each night, ranging from 0 to 29 times, where the higher a number indicates a worse outcome. The ADSS is designed to be completed daily, using a daily diary, with respondents thinking about sleep "last night." Each item is scored individually. LS Means were calculated using a MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by- visit-interaction as fixed continuous effects.

Outcome measures

Outcome measures
Measure	Placebo n=208 Participants Placebo administered orally once daily.	2mg Baricitinib n=103 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=105 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=112 Participants 4mg Baricitinib administered orally once daily.
Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS)	-0.8 units on a scale Standard Error 0.09	-1.10 units on a scale Standard Error 0.12	-1.21 units on a scale Standard Error 0.12	-1.38 units on a scale Standard Error 0.12

SECONDARY outcome

Timeframe: Baseline, 16 Weeks

Population: All randomized participants with a Week 16 Skin Pain NRS data.

Skin Pain NRS is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no pain" and 10 representing "worst pain imaginable." Overall severity of a participant's skin pain is indicated by selecting the number, using a daily diary, that best describes the worst level of skin pain in the past 24 hours. LSMean was calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.

Outcome measures

Outcome measures
Measure	Placebo n=49 Participants Placebo administered orally once daily.	2mg Baricitinib n=31 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=38 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=47 Participants 4mg Baricitinib administered orally once daily.
Change From Baseline in Skin Pain NRS	-0.86 units on a scale Standard Error 0.26	-1.09 units on a scale Standard Error 0.32	-2.61 units on a scale Standard Error 0.30	-2.49 units on a scale Standard Error 0.28

SECONDARY outcome

Timeframe: 16 Weeks

Population: All randomized participants.

The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs (1) erythema, (2)edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2 and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI 50 is defined as ≥50% improvement from baseline in EASI score.

Outcome measures

Outcome measures
Measure	Placebo n=244 Participants Placebo administered orally once daily.	2mg Baricitinib n=125 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=123 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=123 Participants 4mg Baricitinib administered orally once daily.
Percentage of Participants Achieving EASI50	12.3 percentage of participants	18.4 percentage of participants	27.6 percentage of participants	29.3 percentage of participants

SECONDARY outcome

Timeframe: 16 Weeks

Population: All randomized participants.

The IGA measures the investigator's global assessment of the participants overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.

Outcome measures

Outcome measures
Measure	Placebo n=244 Participants Placebo administered orally once daily.	2mg Baricitinib n=125 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=123 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=123 Participants 4mg Baricitinib administered orally once daily.
Percentage of Participants Achieving IGA of 0	1.6 percentage of participants	2.4 percentage of participants	4.1 percentage of participants	4.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 16 Weeks

Population: All randomized participants with a Week 16 SCORAD data.

The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable itching or lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), \& subjective symptoms (C: 0-20) combine using A/5 + 7\*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. LSMeans was calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, \& treatment-by-visit-interaction as fixed categorical effects. Baseline and baseline-by-visit-interaction as fixed continuous effects.

Outcome measures

Outcome measures
Measure	Placebo n=52 Participants Placebo administered orally once daily.	2mg Baricitinib n=34 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=40 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=49 Participants 4mg Baricitinib administered orally once daily.
Change From Baseline in SCORAD	-13.35 units on a scale Standard Error 2.31	-20.23 units on a scale Standard Error 2.84	-27.83 units on a scale Standard Error 2.62	-27.50 units on a scale Standard Error 2.41

SECONDARY outcome

Timeframe: 16 Weeks

Population: All randomized participants.

The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable itching or lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), \& subjective symptoms (C: 0-20) combine using A/5 + 7\*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. SCORAD90 defined as a ≥ 90% improvement from baseline in the SCORAD score.

Outcome measures

Outcome measures
Measure	Placebo n=244 Participants Placebo administered orally once daily.	2mg Baricitinib n=125 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=123 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=123 Participants 4mg Baricitinib administered orally once daily.
Percentage of Participants Achieving SCORAD90	1.2 percentage of participants	3.2 percentage of participants	4.1 percentage of participants	4.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 16 Weeks

Population: All randomized participants with Week 16 BSA data.

Body surface area affected by AD will be assessed for 4 separate body regions and is collected as part of the EASI assessment: head and neck, trunk (including genital region), upper extremities, and lower extremities (including the buttocks). Each body region will be assessed for disease extent ranging from 0% to 100% involvement. The overall total percentage will be reported based off of all 4 body regions combined, after applying specific multipliers to the different body regions to account for the percent of the total BSA represented by each of the 4 regions. Use the percentage of skin affected for each region (0 to 100%) in EASI as follows: BSA Total = 0.1\*BSAhead and neck + 0.3\*BSAtrunk + 0.2\* BSAupper limbs + 0.4\*BSAlower limbs. LSMean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.

Outcome measures

Outcome measures
Measure	Placebo n=52 Participants Placebo administered orally once daily.	2mg Baricitinib n=34 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=40 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=49 Participants 4mg Baricitinib administered orally once daily.
Change From Baseline in Body Surface Area (BSA) Affected	12.82 unit on a scale Standard Error 2.07	-18.98 unit on a scale Standard Error 2.53	-22.12 unit on a scale Standard Error 2.37	-23.98 unit on a scale Standard Error 2.17

SECONDARY outcome

Timeframe: 16 Weeks

Population: All randomized participants.

Percentage of participants developing skin infections requiring antibiotic treatment.

Outcome measures

Outcome measures
Measure	Placebo n=244 Participants Placebo administered orally once daily.	2mg Baricitinib n=124 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=123 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=123 Participants 4mg Baricitinib administered orally once daily.
Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment	7.8 Percentage of participants	4.8 Percentage of participants	7.3 Percentage of participants	4.9 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, 16 Weeks

Population: All randomized participants with week 16 Itch NRS data.

The Itch NRS is a participant-administered, 11-point horizontal scale, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours. LSMean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, \& treatment-by-visit-interaction as fixed categorical effects. Baseline and baseline-by-visit-interaction as fixed continuous effects.

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants Placebo administered orally once daily.	2mg Baricitinib n=31 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=38 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=47 Participants 4mg Baricitinib administered orally once daily.
Percent Change From Baseline in Itch NRS	-16.58 Percent Change Standard Error 5.45	-31.39 Percent Change Standard Error 6.61	47.24 Percent Change Standard Error 6.10	46.87 Percent Change Standard Error 5.43

SECONDARY outcome

Timeframe: Baseline, 16 Weeks

Population: All randomized participants with week 16 POEM data.

The POEM is a 7-item self-assessment questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) on a scale ranging from 0-4 (0 = no days, 1 = 1-2 days, 2 = 3-4 days, 3 = 5-6 days, 4 = everyday). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (severe disease). High scores are indicative of more severe disease and poor quality of life. LSMean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, \& treatment-by-visit-interaction as fixed categorical effects. Baseline and baseline-by-visit-interaction as fixed continuous effects.

Outcome measures

Outcome measures
Measure	Placebo n=52 Participants Placebo administered orally once daily.	2mg Baricitinib n=34 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=40 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=48 Participants 4mg Baricitinib administered orally once daily.
Change From Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM)	-1.48 units on a scale Standard Error 0.84	-3.85 units on a scale Standard Error 1.04	-7.06 units on a scale Standard Error 0.96	-7.56 units on a scale Standard Error 0.88

SECONDARY outcome

Timeframe: Baseline, 16 Weeks

Population: All randomized participants with Week 16 PGI-S-AD data.

The PGI-S-AD asked the participant to evaluate the severity of the disease at that point in time on a single-item, 5-point scale, using a daily diary. The same category labels used in the Physician's Global Assessment were used for the PGI-S-AD, ie, "(0) no symptoms", "(1) very mild", "(2) mild" "(3) moderate", and "(4) severe." LS Means were calculated using a MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.

Outcome measures

Outcome measures
Measure	Placebo n=49 Participants Placebo administered orally once daily.	2mg Baricitinib n=31 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=38 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=47 Participants 4mg Baricitinib administered orally once daily.
Change From Baseline in the Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD) Score	-0.27 units on a scale Standard Error 0.11	-0.53 units on a scale Standard Error 0.14	-0.88 units on a scale Standard Error 0.13	-0.96 units on a scale Standard Error 0.12

SECONDARY outcome

Timeframe: Baseline, 16 Weeks

Population: All randomized participants with Week 16 HADS data.

The HADS is a participant-rated instrument used to assess both anxiety and depression. This instrument consists of 14 items questionnaire, each item is rated on a 4-point scale, giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a significant 'case' of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7, 'normal. LSMean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, \& treatment-by-visit-interaction as fixed categorical effects. Baseline and baseline-by-visit-interaction as fixed continuous effects.

Outcome measures

Outcome measures
Measure	Placebo n=52 Participants Placebo administered orally once daily.	2mg Baricitinib n=34 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=40 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=48 Participants 4mg Baricitinib administered orally once daily.
Change From Baseline on the Hospital Anxiety and Depression Scale (HADS) Anxiety	-0.99 units on a scale Standard Error 0.33	-1.93 units on a scale Standard Error 0.40	-1.92 units on a scale Standard Error 0.38	-2.30 units on a scale Standard Error 0.35
Change From Baseline on the Hospital Anxiety and Depression Scale (HADS) Depression	-0.28 units on a scale Standard Error 0.32	-0.78 units on a scale Standard Error 0.40	-0.99 units on a scale Standard Error 0.37	-1.46 units on a scale Standard Error 0.35

SECONDARY outcome

Timeframe: Baseline, 16 Weeks

Population: All randomized participants with week 16 DLQI data.

The DLQI is a simple, participant-administered, 10 question, validated, quality-of-life questionnaire that covers 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. The recall period of this scale is over the last "week." Response categories include "not at all," "a lot," and "very much," with corresponding scores of 1, 2, and 3, respectively, and unanswered ("not relevant") responses scored as "0." Scores range from 0 to 30 (less to more impairment), and a 4-point change from baseline is considered as the minimal clinically important difference threshold. LSMean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, \& treatment-by-visit-interaction as fixed categorical effects. Baseline and baseline-by-visit-interaction as fixed continuous effects.

Outcome measures

Outcome measures
Measure	Placebo n=52 Participants Placebo administered orally once daily.	2mg Baricitinib n=34 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=40 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=48 Participants 4mg Baricitinib administered orally once daily.
Change From Baseline on the Dermatology Life Quality Index (DLQI)	-3.35 units on a scale Standard Error 0.62	-5.11 units on a scale Standard Error 0.76	-7.44 units on a scale Standard Error 0.71	-7.56 units on a scale Standard Error 0.66

SECONDARY outcome

Timeframe: Baseline, 16 Weeks

Population: All randomized participants with week 16 WPAI-AD data.

The WPAI-AD participant questionnaire was developed to measure the effect of general health and symptom severity on work productivity and regular activities in the 7 days prior to the visit. The WPAI-AD consists of 6 items grouped in 4 domains: absenteeism (work time missed), presenteeism (impairment at work/reduced on-the-job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism), and activity impairment, that range from 0% to 100%, with higher values indicating greater impairment. LSMean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, \& treatment-by-visit-interaction as fixed categorical effects. Baseline and baseline-by-visit-interaction as fixed continuous effects.

Outcome measures

Outcome measures
Measure	Placebo n=52 Participants Placebo administered orally once daily.	2mg Baricitinib n=34 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=39 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=49 Participants 4mg Baricitinib administered orally once daily.
Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire Absenteeism	-4.40 units on a scale Standard Error 3.45	-5.31 units on a scale Standard Error 3.91	-3.39 units on a scale Standard Error 3.68	0.76 units on a scale Standard Error 3.08
Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire Presentisms	-6.15 units on a scale Standard Error 3.87	-9.27 units on a scale Standard Error 4.08	-19.71 units on a scale Standard Error 3.90	-19.28 units on a scale Standard Error 3.37
Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire Work Productivity Loss	-7.15 units on a scale Standard Error 4.65	-8.96 units on a scale Standard Error 4.86	-16.63 units on a scale Standard Error 4.65	-16.28 units on a scale Standard Error 3.96
Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire Activities Impairment	-8.94 units on a scale Standard Error 2.74	-11.21 units on a scale Standard Error 3.34	-23.25 units on a scale Standard Error 3.12	-23.41 units on a scale Standard Error 2.82

SECONDARY outcome

Timeframe: Baseline, 16 Weeks

Population: All randomized participants with week 16 EQ-5D-5L health state index US \& UK data.

EQ-5D-5L is a 2-part measurement. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1. A higher score indicates better health state. LSMean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, \& treatment-by-visit-interaction as fixed categorical effects. Baseline and baseline-by-visit-interaction as fixed continuous effects.

Outcome measures

Outcome measures
Measure	Placebo n=52 Participants Placebo administered orally once daily.	2mg Baricitinib n=34 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=39 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=49 Participants 4mg Baricitinib administered orally once daily.
Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm Health State Index Score (US Algorithm)	0.02 units on a scale Standard Error 0.02	0.05 units on a scale Standard Error 0.02	0.10 units on a scale Standard Error 0.02	0.10 units on a scale Standard Error 0.02
Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm Health State Index Score (UK Algorithm)	0.03 units on a scale Standard Error 0.02	0.06 units on a scale Standard Error 0.03	0.14 units on a scale Standard Error 0.02	0.14 units on a scale Standard Error 0.02

SECONDARY outcome

Timeframe: Baseline, 16 Weeks

Population: All randomized participants with week 16 EQ-5D-5L VAS data.

EQ-5D-5L is a 2-part measurement. The second part is assessed using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine. LSMean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, \& treatment-by-visit-interaction as fixed categorical effects. Baseline and baseline-by-visit-interaction as fixed continuous effects.

Outcome measures

Outcome measures
Measure	Placebo n=52 Participants Placebo administered orally once daily.	2mg Baricitinib n=34 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=39 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=49 Participants 4mg Baricitinib administered orally once daily.
Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS)	2.34 Millimeter (mm) Standard Error 2.22	2.75 Millimeter (mm) Standard Error 2.71	10.54 Millimeter (mm) Standard Error 2.53	11.16 Millimeter (mm) Standard Error 2.30

SECONDARY outcome

Timeframe: 4 Weeks

Population: All randomized participants.

The IGA measures the investigator's global assessment of the participants overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.

Outcome measures

Outcome measures
Measure	Placebo n=244 Participants Placebo administered orally once daily.	2mg Baricitinib n=125 Participants 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=123 Participants 4mg Baricitinib administered orally once daily.	4mg Baricitinib n=123 Participants 4mg Baricitinib administered orally once daily.
Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement	3.7 percentage of participants	3.2 percentage of participants	8.1 percentage of participants	15.4 percentage of participants

Adverse Events

Placebo

Serious events: 9 serious events

Other events: 34 other events

Deaths: 0 deaths

1mg Baricitinib

Serious events: 9 serious events

Other events: 23 other events

Deaths: 0 deaths

2mg Baricitinib

Serious events: 3 serious events

Other events: 27 other events

Deaths: 0 deaths

4mg Baricitinib

Serious events: 1 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=244 participants at risk Placebo administered orally once daily.	1mg Baricitinib n=124 participants at risk 1 milligram (mg) Baricitinib administered orally once daily.	2mg Baricitinib n=123 participants at risk 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=123 participants at risk 4mg Baricitinib administered orally once daily.
Infections and infestations Herpes simplex	0.82% 2/244 • Number of events 3 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	1.6% 2/124 • Number of events 2 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	5.7% 7/123 • Number of events 7 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	2.4% 3/123 • Number of events 3 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	12.3% 30/244 • Number of events 33 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	10.5% 13/124 • Number of events 13 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	13.0% 16/123 • Number of events 16 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	8.1% 10/123 • Number of events 12 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.
Investigations Blood creatine phosphokinase increased	0.41% 1/244 • Number of events 1 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	3.2% 4/124 • Number of events 4 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.81% 1/123 • Number of events 1 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	5.7% 7/123 • Number of events 7 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.
Nervous system disorders Headache	2.0% 5/244 • Number of events 8 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	4.8% 6/124 • Number of events 6 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	7.3% 9/123 • Number of events 9 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	8.9% 11/123 • Number of events 14 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Placebo n=244 participants at risk Placebo administered orally once daily.	1mg Baricitinib n=124 participants at risk 1 milligram (mg) Baricitinib administered orally once daily.	2mg Baricitinib n=123 participants at risk 2mg Baricitinib administered orally once daily.	4mg Baricitinib n=123 participants at risk 4mg Baricitinib administered orally once daily.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/244 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.81% 1/124 • Number of events 1 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.
Eye disorders Cataract	0.00% 0/244 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.81% 1/124 • Number of events 1 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.
Eye disorders Retinal detachment	0.41% 1/244 • Number of events 1 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/124 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Diverticulum	0.00% 0/244 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.81% 1/124 • Number of events 1 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.
Infections and infestations Eczema herpeticum	0.82% 2/244 • Number of events 2 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	1.6% 2/124 • Number of events 2 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.
Infections and infestations Encephalitis viral	0.00% 0/244 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.81% 1/124 • Number of events 1 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.
Infections and infestations Peritonsillitis	0.00% 0/244 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.81% 1/124 • Number of events 1 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.
Infections and infestations Tonsillitis	0.00% 0/244 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/124 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.81% 1/123 • Number of events 1 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.41% 1/244 • Number of events 1 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/124 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.
Psychiatric disorders Depression	0.00% 0/244 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/124 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.81% 1/123 • Number of events 1 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.
Psychiatric disorders Panic attack	0.00% 0/244 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/124 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.81% 1/123 • Number of events 1 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/244 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.81% 1/124 • Number of events 1 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/244 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.81% 1/124 • Number of events 1 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dermatitis atopic	1.2% 3/244 • Number of events 3 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.81% 1/124 • Number of events 1 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.81% 1/123 • Number of events 1 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dermatitis exfoliative generalised	0.41% 1/244 • Number of events 1 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/124 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Drug eruption	0.00% 0/244 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.81% 1/124 • Number of events 1 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.
Vascular disorders Hypertension	0.41% 1/244 • Number of events 1 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/124 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/123 • Baseline to end of study (Up to 20 weeks) All randomized participants who received at least one dose of study drug.