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Clinical Trial Results:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib in Patients with Moderate to Severe Atopic Dermatitis

Summary
EudraCT number	2017-000871-10
Trial protocol	HU AT ES PL
Global end of trial date	12 Dec 2018

Results information
Results version number	v1(current)
This version publication date	27 Dec 2019
First version publication date	27 Dec 2019
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

I4V-MC-JAHM

ISRCTN number

US NCT number

NCT03334422

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 16581

Sponsor organisation name

Eli Lilly and Company

Sponsor organisation address

Lilly Corporate Center, Indianapolis, IN, United States, 46285

Public contact

Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,

Scientific contact

Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

12 Dec 2018

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

12 Dec 2018

Was the trial ended prematurely?

Main objective of the trial

The purpose of this study is to evaluate the efficacy and safety of baricitinib as monotherapy in participants with moderate to severe atopic dermatitis.

Protection of trial subjects

This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.

Background therapy

Evidence for comparator

Actual start date of recruitment

27 Nov 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 67

Country: Number of subjects enrolled

Korea, Republic of: 55

Country: Number of subjects enrolled

Austria: 31

Country: Number of subjects enrolled

Hungary: 52

Country: Number of subjects enrolled

Japan: 112

Country: Number of subjects enrolled

Poland: 118

Country: Number of subjects enrolled

Israel: 34

Country: Number of subjects enrolled

Australia: 67

Country: Number of subjects enrolled

Switzerland: 25

Country: Number of subjects enrolled

Spain: 54

Worldwide total number of subjects

615

EEA total number of subjects

255

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

596

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

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

Screening details

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo

Arm description

Placebo administered orally once daily.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo administered orally once daily.

1mg Baricitinib

Arm description

1 milligram (mg) Baricitinib administered orally once daily.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

Other name

LY3009104

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

1mg Baricitinib administered orally once daily.

2mg Baricitinib

Arm description

2mg Baricitinib administered orally once daily.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

Other name

LY3009104

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

2mg Baricitinib administered orally once daily.

4mg Baricitinib

Arm description

4mg Baricitinib administered orally once daily.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

Other name

LY3009104

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

4mg Baricitinib administered orally once daily.

Number of subjects in period 1	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Started	244	125	123	123
Received at least one dose of study drug	244	124	123	123
Completed	225	115	113	117
Not completed	19	10	10	6
Consent withdrawn by subject	8	3	1	-
Adverse event, non-fatal	1	3	2	2
inability to obtain laboratory samples	-	1	-	-
Pregnancy	-	1	-	-
Lost to follow-up	-	-	-	1
Lack of efficacy	10	2	7	3

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Placebo administered orally once daily.

Reporting group title

1mg Baricitinib

Reporting group description

1 milligram (mg) Baricitinib administered orally once daily.

Reporting group title

2mg Baricitinib

Reporting group description

2mg Baricitinib administered orally once daily.

Reporting group title

4mg Baricitinib

Reporting group description

4mg Baricitinib administered orally once daily.

Reporting group values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib	Total
Number of subjects	244	125	123	123	615
Age categorical
Units: Subjects
In utero	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0
Adults (18-64 years)	235	124	118	119	596
From 65-84 years	9	1	5	4	19
85 years and over	0	0	0	0	0
Gender categorical
Units: Subjects
Female	90	45	58	41	234
Male	154	80	65	82	381
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0
Asian	72	36	37	38	183
Native Hawaiian or Other Pacific Islander	0	1	0	0	1
Black or African American	0	0	0	0	0
White	169	85	85	82	421
More than one race	3	3	1	3	10
Unknown or Not Reported	0	0	0	0	0
Region of Enrollment
Units: Subjects
Argentina	28	14	13	12	67
South Korea	24	11	11	9	55
Austria	13	7	4	7	31
Hungary	23	10	11	8	52
Japan	45	22	22	23	112
Poland	41	27	21	29	118
Israel	12	7	6	9	34
Australia	24	14	15	14	67
Switzerland	13	5	5	2	25
Spain	21	8	15	10	54

End points

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Reporting group title

Placebo

Reporting group description

Placebo administered orally once daily.

Reporting group title

1mg Baricitinib

Reporting group description

1 milligram (mg) Baricitinib administered orally once daily.

Reporting group title

2mg Baricitinib

Reporting group description

2mg Baricitinib administered orally once daily.

Reporting group title

4mg Baricitinib

Reporting group description

4mg Baricitinib administered orally once daily.

Primary: Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 with a ≥ 2 Point Improvement (Placebo, 2mg and 4 mg Baricitinib)

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End point title

Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 with a ≥ 2 Point Improvement (Placebo, 2mg and 4 mg Baricitinib) ^[1]

End point description

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

End point type

Primary

End point timeframe

16 Weeks

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, the primary outcome measure was to compare the response in participants who received the 2 mg and 4 mg doses of Baricitinib to the response of participants who received placebo.

End point values	Placebo	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	244	123	123
Units: percentage of participants
number (not applicable)	4.5	10.6	13.8

IGA of 0 or 1: 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.026

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.58

Confidence interval

level

95%

sides

2-sided

lower limit

1.12

upper limit

5.92

IGA of 0 or 1: 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.64

Confidence interval

level

95%

sides

2-sided

lower limit

1.64

upper limit

8.05

Secondary: Percentage of Participants Achieving IGA of 0 or 1 with a ≥ 2 Point Improvement (Placebo, 1mg Baricitinib)

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End point title

Percentage of Participants Achieving IGA of 0 or 1 with a ≥ 2 Point Improvement (Placebo, 1mg Baricitinib) ^[2]

End point description

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

End point type

Secondary

End point timeframe

16 Weeks

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, the secondary outcome measure was to compare the response in participants who received the 1 mg dose of Baricitinib to the response of participants who received placebo.

End point values	Placebo	1mg Baricitinib
Number of subjects analysed	244	125
Units: percentage of participants
number (not applicable)	4.5	8.8

IGA of 0 or 1 - 1mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

369

Analysis specification

Pre-specified

Analysis type

superiority

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

5.02

Secondary: Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75)

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End point title

Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75)

End point description

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 and 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. APD:All randomized participants.

End point type

Secondary

End point timeframe

16 Weeks

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	244	125	123	123
Units: percentage of participants
number (not applicable)	6.1	12.8	17.9	21.1

EASI75 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

369

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.024

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.35

Confidence interval

level

95%

sides

2-sided

lower limit

1.12

upper limit

4.93

EASI75 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.49

Confidence interval

level

95%

sides

2-sided

lower limit

1.73

upper limit

7.04

EASI75 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.41

Confidence interval

level

95%

sides

2-sided

lower limit

2.22

upper limit

8.76

Secondary: Percentage of Participants Achieving EASI90

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End point title

Percentage of Participants Achieving EASI90

End point description

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 and 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. APD: All randomized participants.

End point type

Secondary

End point timeframe

16 Weeks

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	244	125	123	123
Units: percentage of participants
number (not applicable)	2.5	6.4	8.9	13.0

EASI90 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

369

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.053

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

7.97

EASI90 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.007

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.87

Confidence interval

level

95%

sides

2-sided

lower limit

1.44

upper limit

10.41

EASI90 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

6.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.42

upper limit

15.91

Secondary: Percent Change from Baseline (PFCB) on EASI Score

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End point title

Percent Change from Baseline (PFCB) on EASI Score

End point description

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 and 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.

End point type

Secondary

End point timeframe

Baseline, 16 Weeks APD: All randomized participants who had a week 16 EASI data.

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	52	34	40	49
Units: Percent Change
least squares mean (standard error)	-28.91 ( 4.32 )	-41.68 ( 5.33 )	-54.80 ( 4.99 )	-54.88 ( 4.56 )

PCFB EASI - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.062

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-12.76

Confidence interval

level

95%

sides

2-sided

lower limit

-26.19

upper limit

0.66

Variability estimate

Standard error of the mean

Dispersion value

6.81

PCFB EASI - 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-25.89

Confidence interval

level

95%

sides

2-sided

lower limit

-38.78

upper limit

-12.99

Variability estimate

Standard error of the mean

Dispersion value

6.54

PCFB EASI - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-25.97

Confidence interval

level

95%

sides

2-sided

lower limit

-38.29

upper limit

-13.65

Variability estimate

Standard error of the mean

Dispersion value

6.24

Secondary: Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75)

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End point title

Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75)

End point description

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. APD: All randomized participants.

End point type

Secondary

End point timeframe

16 Weeks

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	244	125	123	123
Units: percentage of participants
number (not applicable)	1.6	4.8	7.3	11.4

SCORAD 75 - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

369

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.086

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

9.76

SCORAD 75 - 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.95

Confidence interval

level

95%

sides

2-sided

lower limit

1.58

upper limit

15.49

SCORAD 75 - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

7.4

Confidence interval

level

95%

sides

2-sided

lower limit

2.51

upper limit

21.83

Secondary: Percentage of Participants Achieving a 4-Point Improvement on the Itch Numeric Rating Scale (NRS)

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End point title

Percentage of Participants Achieving a 4-Point Improvement on the Itch Numeric Rating Scale (NRS)

End point description

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

End point type

Secondary

End point timeframe

16 Weeks

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	213	100	106	107
Units: percentage of participants
number (not applicable)	4.7	6.0	15.1	18.7

Itch NRS - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.505

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.41

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

3.87

Itch NRS - 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

319

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.64

Confidence interval

level

95%

sides

2-sided

lower limit

1.6

upper limit

8.27

Itch NRS - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.91

Confidence interval

level

95%

sides

2-sided

lower limit

2.22

upper limit

10.86

Secondary: Change from Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS)

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End point title

Change from Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS)

End point description

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. 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.

End point type

Secondary

End point timeframe

Baseline, 16 Weeks APD: All randomized participants with a Week 16 ADSS Item 2 (frequency of waking) data.

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	208	103	105	112
Units: units on a scale
least squares mean (standard error)	-0.8 ( 0.09 )	-1.10 ( 0.12 )	-1.21 ( 0.12 )	-1.38 ( 0.12 )

CFB ADSS - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.074

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-0.27

Confidence interval

level

95%

sides

2-sided

lower limit

-0.57

upper limit

0.03

Variability estimate

Standard error of the mean

Dispersion value

0.15

CFB ADSS - 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.011

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-0.38

Confidence interval

level

95%

sides

2-sided

lower limit

-0.68

upper limit

-0.09

Variability estimate

Standard error of the mean

Dispersion value

0.15

CFB ADSS - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-0.55

Confidence interval

level

95%

sides

2-sided

lower limit

-0.84

upper limit

-0.26

Variability estimate

Standard error of the mean

Dispersion value

0.15

Secondary: Change from Baseline in Skin Pain NRS

Top of page

End point title

Change from Baseline in Skin Pain NRS

End point description

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

End point type

Secondary

End point timeframe

Baseline, 16 Weeks

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	49	31	38	47
Units: units on a scale
least squares mean (standard error)	-0.86 ( 0.26 )	-1.09 ( 0.32 )	-2.61 ( 0.30 )	-2.49 ( 0.28 )

CFB Skin Pain NRS - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.58

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-0.23

Confidence interval

level

95%

sides

2-sided

lower limit

-1.05

upper limit

0.59

Variability estimate

Standard error of the mean

Dispersion value

0.41

CFB Skin Pain NRS - 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-1.75

Confidence interval

level

95%

sides

2-sided

lower limit

-2.54

upper limit

-0.96

Variability estimate

Standard error of the mean

Dispersion value

0.4

CFB Skin Pain NRS - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-1.62

Confidence interval

level

95%

sides

2-sided

lower limit

-2.37

upper limit

-0.87

Variability estimate

Standard error of the mean

Dispersion value

0.38

Secondary: Percentage of Participants Achieving EASI50

Top of page

End point title

Percentage of Participants Achieving EASI50

End point description

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 and neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2 and 3. Each body site will have a score that ranges from 0 to 72, and the final EASI score was obtained by weight-averaging these 4 scores. Hence, the final EASI score will range from 0 to 72 (Severe). The EASI 50 is defined as ≥50% improvement from baseline in EASI score. APD: All randomized participants.

End point type

Secondary

End point timeframe

16 Weeks

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	244	125	123	123
Units: percentage of participants
number (not applicable)	12.3	18.4	27.6	29.3

EASI50 - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

369

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.094

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.67

Confidence interval

level

95%

sides

2-sided

lower limit

0.92

upper limit

3.04

EASI50 - 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.91

Confidence interval

level

95%

sides

2-sided

lower limit

1.65

upper limit

5.11

EASI50 - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.15

Confidence interval

level

95%

sides

2-sided

lower limit

1.8

upper limit

5.51

Secondary: Percentage of Participants Achieving IGA of 0

Top of page

End point title

Percentage of Participants Achieving IGA of 0

End point description

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.

End point type

Secondary

End point timeframe

16 Weeks

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	244	125	123	123
Units: percentage of participants
number (not applicable)	1.6	2.4	4.1	4.1

IGA of 0 - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

369

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.528

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.57

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

6.31

IGA of 0 - 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.142

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.56

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

8.95

IGA of 0 - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.123

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.68

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

9.37

Secondary: Change from Baseline in SCORing Atopic Dermatitis (SCORAD)

Top of page

End point title

Change from Baseline in SCORing Atopic Dermatitis (SCORAD)

End point description

SCORAD index uses the rule of nines to assess disease extent & evaluates 6 clinical characteristics to determine disease severity: (1) erythema (2) edema/papulation (3) oozing/crusts (4) excoriation (5) lichenification & (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). SCORAD index also assesses subjective symptoms of pruritus & sleep loss with VAS where 0 is no itching or no trouble sleeping & 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. LSMean was calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, & treatment-by-visit-interaction as fixed categorical effects. Baseline & baseline-by-visit-interaction as fixed continuous effects. APD: All randomized participants with a Week 16 SCORAD data.

End point type

Secondary

End point timeframe

Baseline, 16 Weeks

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	52	34	40	49
Units: units on a scale
least squares mean (standard error)	-13.35 ( 2.31 )	-20.23 ( 2.84 )	-27.83 ( 2.62 )	-27.50 ( 2.41 )

CFB SCORAD - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.059

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-6.88

Confidence interval

level

95%

sides

2-sided

lower limit

-14.03

upper limit

0.28

Variability estimate

Standard error of the mean

Dispersion value

3.63

CFB SCORAD - 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-14.48

Confidence interval

level

95%

sides

2-sided

lower limit

-21.32

upper limit

-7.63

Variability estimate

Standard error of the mean

Dispersion value

3.47

CFB SCORAD - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-14.15

Confidence interval

level

95%

sides

2-sided

lower limit

-20.69

upper limit

-7.61

Variability estimate

Standard error of the mean

Dispersion value

3.32

Secondary: Percentage of Participants Achieving SCORAD90

Top of page

End point title

Percentage of Participants Achieving SCORAD90

End point description

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. APD: All randomized participants.

End point type

Secondary

End point timeframe

16 Weeks

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	244	125	123	123
Units: percentage of participants
number (not applicable)	1.2	3.2	4.1	4.9

SCORAD90 - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

369

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.193

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.55

Confidence interval

level

95%

sides

2-sided

lower limit

0.62

upper limit

10.45

SCORAD90 - 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.042

Method

Mixed models analysis

Parameter type

Odds ratio (OR)

Point estimate

4.1

Confidence interval

level

95%

sides

2-sided

lower limit

1.05

upper limit

16.03

SCORAD90 - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.044

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.89

Confidence interval

level

95%

sides

2-sided

lower limit

1.04

upper limit

14.57

Secondary: Change from Baseline in Body Surface Area (BSA) Affected

Top of page

End point title

Change from Baseline in Body Surface Area (BSA) Affected

End point description

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.

End point type

Secondary

End point timeframe

Baseline, 16 Weeks APD: All randomized participants with week 16 BSA.

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	52	34	40	49
Units: units on a scale
median (standard error)	12.82 ( 2.07 )	-18.98 ( 2.53 )	-22.12 ( 2.37 )	-23.98 ( 2.17 )

CFB BSA - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.058

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-6.16

Confidence interval

level

95%

sides

2-sided

lower limit

-12.53

upper limit

0.21

Variability estimate

Standard error of the mean

Dispersion value

3.23

CFB BSA - 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-9.3

Confidence interval

level

95%

sides

2-sided

lower limit

-15.42

upper limit

-3.18

Variability estimate

Standard error of the mean

Dispersion value

3.1

CFB BSA - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-11.16

Confidence interval

level

95%

sides

2-sided

lower limit

-17.03

upper limit

-5.3

Variability estimate

Standard error of the mean

Dispersion value

2.98

Secondary: Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment

Top of page

End point title

Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment

End point description

Number of participants developing skin infections requiring antibiotic treatment. APD: All randomized participants.

End point type

Secondary

End point timeframe

16 Weeks

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	244	125	123	123
Units: Percentage of participants
number (not applicable)	7.8	4.8	7.3	4.9

Skin Infections - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

369

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.189

Method

Fisher exact

Confidence interval

Skin Infections - 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 1

Method

Fisher exact

Confidence interval

Skin Infections - 4 mg Baricitinib

Comparison groups

4mg Baricitinib v Placebo

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.383

Method

Fisher exact

Confidence interval

Secondary: Percent Change from Baseline in Itch NRS

Top of page

End point title

Percent Change from Baseline in Itch NRS

End point description

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

End point type

Secondary

End point timeframe

Baseline, 16 Weeks

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	48	31	38	47
Units: Percent Change
least squares mean (standard error)	-16.58 ( 5.45 )	-31.39 ( 6.61 )	47.24 ( 6.10 )	46.87 ( 5.43 )

PCFB Itch NRS - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.081

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-14.8

Confidence interval

level

95%

sides

2-sided

lower limit

-31.45

upper limit

1.85

Variability estimate

Standard error of the mean

Dispersion value

8.46

PCFB Itch NRS - 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-30.66

Confidence interval

level

95%

sides

2-sided

lower limit

-46.62

upper limit

-14.7

Variability estimate

Standard error of the mean

Dispersion value

8.11

PCFB Itch NRS - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-30.28

Confidence interval

level

95%

sides

2-sided

lower limit

-45.29

upper limit

-15.27

Variability estimate

Standard error of the mean

Dispersion value

7.63

Secondary: Change from Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM)

Top of page

End point title

Change from Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM)

End point description

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. APD: All randomized participants with week 16 POEM data.

End point type

Secondary

End point timeframe

Baseline, 16 Weeks

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	52	34	40	48
Units: units on a scale
least squares mean (standard error)	-1.48 ( 0.84 )	-3.85 ( 1.04 )	-7.06 ( 0.96 )	-7.56 ( 0.88 )

CFB POEM - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.075

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-2.36

Confidence interval

level

95%

sides

2-sided

lower limit

-4.97

upper limit

0.24

Variability estimate

Standard error of the mean

Dispersion value

1.32

CFB POEM - 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-5.58

Confidence interval

level

95%

sides

2-sided

lower limit

-8.07

upper limit

-3.08

Variability estimate

Standard error of the mean

Dispersion value

1.27

CFB POEM - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-6.07

Confidence interval

level

95%

sides

2-sided

lower limit

-8.47

upper limit

-3.68

Variability estimate

Standard error of the mean

Dispersion value

1.21

Secondary: Change from Baseline in the Patient Global Impression of Severity—Atopic Dermatitis (PGI-S-AD) Score

Top of page

End point title

Change from Baseline in the Patient Global Impression of Severity—Atopic Dermatitis (PGI-S-AD) Score

End point description

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 was used for the PGI-S-AD, ie, "No symptoms (0)", "Very mild (1)", "mild (2)", "moderate (3)", "severe (4)". 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. APD: All randomized participants with Week 16 PGI-S-AD data.

End point type

Secondary

End point timeframe

Baseline, 16 Weeks

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	49	31	38	47
Units: units on a scale
least squares mean (standard error)	-0.27 ( 0.11 )	-0.53 ( 0.14 )	-0.88 ( 0.13 )	-0.96 ( 0.12 )

CFB PGI-S-AD - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.13

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.27

Confidence interval

level

95%

sides

2-sided

lower limit

-0.61

upper limit

0.08

Variability estimate

Standard error of the mean

Dispersion value

0.17

CFB PGI-S-AD - 2mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.61

Confidence interval

level

95%

sides

2-sided

lower limit

-0.94

upper limit

-0.28

Variability estimate

Standard error of the mean

Dispersion value

0.17

CFB PGI-S-AD - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.69

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

-0.38

Variability estimate

Standard error of the mean

Dispersion value

0.16

Secondary: Change from Baseline on the Hospital Anxiety Depression Scale (HADS)

Top of page

End point title

Change from Baseline on the Hospital Anxiety Depression Scale (HADS)

End point description

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. APD: All randomized participants with week 16 HADS data.

End point type

Secondary

End point timeframe

Baseline, 16 Weeks

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	52	34	40	48
Units: units on a scale
least squares mean (standard error)
Anxiety	-0.99 ( 0.33 )	-1.93 ( 0.40 )	-1.92 ( 0.38 )	-2.30 ( 0.35 )
Depression	-0.28 ( 0.32 )	-0.78 ( 0.40 )	-0.99 ( 0.38 )	-1.46 ( 0.35 )

CFB HADS Anxiety - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

= 0.067

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.94

Confidence interval

level

95%

sides

2-sided

lower limit

-1.95

upper limit

0.07

Variability estimate

Standard error of the mean

Dispersion value

0.51

Notes
[3] - HADS Anxiety.

CFB HADS Anxiety - 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[4]

P-value

= 0.06

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.93

Confidence interval

level

95%

sides

2-sided

lower limit

-1.89

upper limit

0.04

Variability estimate

Standard error of the mean

Dispersion value

0.49

Notes
[4] - HADS Anxiety.

CFB HADS Anxiety - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

= 0.006

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2.23

upper limit

-0.38

Variability estimate

Standard error of the mean

Dispersion value

0.47

Notes
[5] - HADS Anxiety.

CFB HADS Depression - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[6]

P-value

= 0.321

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

0.49

Variability estimate

Standard error of the mean

Dispersion value

0.51

Notes
[6] - HADS Depression.

CFB HADS Depression - 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[7]

P-value

= 0.143

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.71

Confidence interval

level

95%

sides

2-sided

lower limit

-1.67

upper limit

0.24

Variability estimate

Standard error of the mean

Dispersion value

0.49

Notes
[7] - HADS Depression.

CFB HADS Depression - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

superiority ^[8]

P-value

= 0.012

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-1.18

Confidence interval

level

95%

sides

2-sided

lower limit

-2.11

upper limit

-0.26

Variability estimate

Standard error of the mean

Dispersion value

0.47

Notes
[8] - HADS Depression.

Secondary: Change from Baseline on the Dermatology Life Quality Index (DLQI)

Top of page

End point title

Change from Baseline on the Dermatology Life Quality Index (DLQI)

End point description

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." Totals 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. APD: All randomized participants with week 16 DLQI data.

End point type

Secondary

End point timeframe

Baseline, 16 Weeks

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	52	34	40	48
Units: units on a scale
least squares mean (standard error)	-3.35 ( 0.62 )	-5.11 ( 0.76 )	-7.44 ( 0.71 )	-7.56 ( 0.66 )

CFB DLQI - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.071

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-1.76

Confidence interval

level

95%

sides

2-sided

lower limit

-3.67

upper limit

0.15

Variability estimate

Standard error of the mean

Dispersion value

0.97

CFB DLQI - 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-4.09

Confidence interval

level

95%

sides

2-sided

lower limit

-5.92

upper limit

-2.26

Variability estimate

Standard error of the mean

Dispersion value

0.93

CFB DLQI - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-4.22

Confidence interval

level

95%

sides

2-sided

lower limit

-5.98

upper limit

-2.45

Variability estimate

Standard error of the mean

Dispersion value

0.9

Secondary: Change from Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire

Top of page

End point title

Change from Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire

End point description

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

End point type

Secondary

End point timeframe

Baseline, 16 Weeks

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	52 ^[9]	34 ^[10]	39 ^[11]	49 ^[12]
Units: units on a scale
least squares mean (standard error)
Absenteeism(25,21,22,33)	-4.40 ( 3.45 )	-5.31 ( 3.91 )	-3.39 ( 3.68 )	0.76 ( 3.08 )
Presenteeism(23,21,22,32)	-6.15 ( 3.87 )	-9.27 ( 4.08 )	-19.71 ( 3.90 )	-19.28 ( 3.37 )
Work Productivity Loss(23,21,22,32)	-7.15 ( 4.65 )	-8.96 ( 4.86 )	-16.63 ( 4.65 )	-16.28 ( 3.96 )
Activity Impairment(52,34,39,49)	-8.94 ( 2.74 )	-11.21 ( 3.34 )	-23.25 ( 3.12 )	-23.41 ( 2.82 )

Notes
[9] - N=25,23,23,52.
[10] - N=21,21,21,34.
[11] - N=22,22,22,39.
[12] - N=33,32,32,49.

CFB Absenteeism - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[13]

P-value

= 0.861

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.91

Confidence interval

level

95%

sides

2-sided

lower limit

-11.16

upper limit

9.34

Variability estimate

Standard error of the mean

Dispersion value

5.17

Notes
[13] - Percentage of Absenteeism Change from Baseline.

CFB Absenteeism - 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[14]

P-value

= 0.841 ^[15]

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

-8.94

upper limit

10.97

Variability estimate

Standard error of the mean

Dispersion value

5.03

Notes
[14] - Percentage of Absenteeism Change from Baseline.
[15] - Absenteeism

CFB Absenteeism - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority ^[16]

P-value

= 0.264

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

5.16

Confidence interval

level

95%

sides

2-sided

lower limit

-3.95

upper limit

14.26

Variability estimate

Standard error of the mean

Dispersion value

4.6

Notes
[16] - Percentage of Absenteeism Change from Baseline.

CFB Presenteeism - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.58

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-3.12

Confidence interval

level

95%

sides

2-sided

lower limit

-14.26

upper limit

8.02

Variability estimate

Standard error of the mean

Dispersion value

5.63

CFB Presenteeism - 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.015

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-13.56

Confidence interval

level

95%

sides

2-sided

lower limit

-24.45

upper limit

-2.86

Variability estimate

Standard error of the mean

Dispersion value

5.5

CFB Presenteeism - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.011

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-13.13

Confidence interval

level

95%

sides

2-sided

lower limit

-23.2

upper limit

-3.06

Variability estimate

Standard error of the mean

Dispersion value

5.08

CFB Work Productivity Loss - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.788

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-1.81

Confidence interval

level

95%

sides

2-sided

lower limit

-15.12

upper limit

11.49

Variability estimate

Standard error of the mean

Dispersion value

6.71

CFB Work Productivity Loss - 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.152

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-9.48

Confidence interval

level

95%

sides

2-sided

lower limit

-22.51

upper limit

3.55

Variability estimate

Standard error of the mean

Dispersion value

6.57

CFB Work Productivity Loss - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.135

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-9.13

Confidence interval

level

95%

sides

2-sided

lower limit

-21.17

upper limit

2.9

Variability estimate

Standard error of the mean

Dispersion value

6.07

CFB Activity Impairment - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.595

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-2.26

Confidence interval

level

95%

sides

2-sided

lower limit

-10.65

upper limit

6.12

Variability estimate

Standard error of the mean

Dispersion value

4.25

CFB Activity Impairment - 2 mg Baricitinib

Comparison groups

2mg Baricitinib v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-14.3

Confidence interval

level

95%

sides

2-sided

lower limit

-22.43

upper limit

-6.17

Variability estimate

Standard error of the mean

Dispersion value

4.12

CFB Activity Impairment - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-14.47

Confidence interval

level

95%

sides

2-sided

lower limit

-22.11

upper limit

-6.83

Variability estimate

Standard error of the mean

Dispersion value

3.88

Secondary: Change From Baseline on the European Quality of Life–5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm

Top of page

End point title

Change From Baseline on the European Quality of Life–5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm

End point description

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. LSMean was calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, & treatment-by-visit-interaction as fixed categorical effects. Baseline and

End point type

Secondary

End point timeframe

Baseline, 16 weeks APD:All randomized participants with week 16 EQ-5D-5L health state index US & UK score.

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	52	34	39	49
Units: units on a scale
least squares mean (standard deviation)
Health State Index Score (US Algorithm)	0.02 ( 0.02 )	0.05 ( 0.02 )	0.10 ( 0.02 )	0.10 ( 0.02 )
Health State Index Score (UK Algorithm)	0.03 ( 0.02 )	0.06 ( 0.03 )	0.14 ( 0.02 )	0.14 ( 0.02 )

CFB Health State Index US - 1 mg Baricitinib

Statistical analysis description

Health State Index Score (US Algorithm)

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.295

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.02

upper limit

0.07

Variability estimate

Standard error of the mean

Dispersion value

0.02

CFB Health State Index US - 2 mg Baricitinib

Statistical analysis description

Health State Index Score (US Algorithm)

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

0.08

Confidence interval

level

95%

sides

2-sided

lower limit

0.03

upper limit

0.12

Variability estimate

Standard error of the mean

Dispersion value

0.02

CFB Health State Index US - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

0.08

Confidence interval

level

95%

sides

2-sided

lower limit

0.03

upper limit

0.12

Variability estimate

Standard error of the mean

Dispersion value

0.02

CFB Health State Index UK - 1 mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.334

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.03

upper limit

0.1

Variability estimate

Standard error of the mean

Dispersion value

0.03

CFB Health State Index UK - 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

0.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.04

upper limit

0.17

Variability estimate

Standard error of the mean

Dispersion value

0.03

CFB Health State Index UK - 4 mg Baricitinib

Statistical analysis description

Health State Index Score (UK Algorithm)

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

0.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.05

upper limit

0.17

Variability estimate

Standard error of the mean

Dispersion value

0.03

Secondary: Change From Baseline on the European Quality of Life–5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS)

Top of page

End point title

Change From Baseline on the European Quality of Life–5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS)

End point description

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

End point type

Secondary

End point timeframe

Baseline, 16 weeks

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	52	34	39	49
Units: Millimeter (mm)
least squares mean (standard error)	2.34 ( 2.22 )	2.75 ( 2.71 )	10.54 ( 2.53 )	11.16 ( 2.30 )

CFB EQ-5D-5L VAS - 1mg Baricitinib

Comparison groups

Placebo v 1mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.907

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-6.44

upper limit

7.25

Variability estimate

Standard error of the mean

Dispersion value

3.47

CFB EQ-5D-5L VAS - 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.015

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

8.19

Confidence interval

level

95%

sides

2-sided

lower limit

1.63

upper limit

14.76

Variability estimate

Standard error of the mean

Dispersion value

3.33

CFB EQ-5D-5L VAS - 4 mg Baricitinib

Comparison groups

Placebo v 4mg Baricitinib

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

8.82

Confidence interval

level

95%

sides

2-sided

lower limit

2.62

upper limit

15.01

Variability estimate

Standard error of the mean

Dispersion value

3.14

Secondary: Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement

Top of page

End point title

Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement

End point description

End point type

Secondary

End point timeframe

4 Weeks

End point values	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Number of subjects analysed	244	125	123	123
Units: percentage of participants
number (not applicable)	3.7	3.2	8.1	15.4

IGA of 0 or 1 (Wk 4): 1 mg Baricitinib

Comparison groups

1mg Baricitinib v Placebo

Number of subjects included in analysis

369

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.905

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

2.93

IGA of 0 or 1 (Wk 4): 2 mg Baricitinib

Comparison groups

Placebo v 2mg Baricitinib

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.064

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.37

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

5.92

IGA of 0 or 1 (Wk 4): 4 mg Baricitinib

Comparison groups

4mg Baricitinib v Placebo

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.01

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.14

Confidence interval

level

95%

sides

2-sided

lower limit

2.25

upper limit

11.74

Adverse events

Top of page

Timeframe for reporting adverse events

Baseline to end of study (Up to 20 weeks)

Adverse event reporting additional description

All randomized participants who received at least one dose of study drug.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.1

Reporting group title

Placebo

Reporting group description

Placebo administered orally once daily.

Reporting group title

1mg Baricitinib

Reporting group description

1mg Baricitinib administered orally once daily.

Reporting group title

2mg Baricitinib

Reporting group description

2mg Baricitinib administered orally once daily.

Reporting group title

4mg Baricitinib

Reporting group description

4mg Baricitinib administered orally once daily.

Serious adverse events	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Total subjects affected by serious adverse events
subjects affected / exposed	9 / 244 (3.69%)	9 / 124 (7.26%)	3 / 123 (2.44%)	1 / 123 (0.81%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Vascular disorders
hypertension
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	1 / 244 (0.41%)	0 / 124 (0.00%)	0 / 123 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
lymphadenopathy
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 244 (0.00%)	1 / 124 (0.81%)	0 / 123 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
cataract
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 244 (0.00%)	1 / 124 (0.81%)	0 / 123 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
retinal detachment
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	1 / 244 (0.41%)	0 / 124 (0.00%)	0 / 123 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
diverticulum
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 244 (0.00%)	1 / 124 (0.81%)	0 / 123 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
asthma
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 244 (0.00%)	1 / 124 (0.81%)	0 / 123 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
angioedema
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 244 (0.00%)	1 / 124 (0.81%)	0 / 123 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
dermatitis atopic
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	3 / 244 (1.23%)	1 / 124 (0.81%)	1 / 123 (0.81%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
dermatitis exfoliative generalised
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	1 / 244 (0.41%)	0 / 124 (0.00%)	0 / 123 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
drug eruption
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 244 (0.00%)	1 / 124 (0.81%)	0 / 123 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
depression
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 244 (0.00%)	0 / 124 (0.00%)	1 / 123 (0.81%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
panic attack
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 244 (0.00%)	0 / 124 (0.00%)	1 / 123 (0.81%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
intervertebral disc protrusion
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	1 / 244 (0.41%)	0 / 124 (0.00%)	0 / 123 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
eczema herpeticum
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	2 / 244 (0.82%)	2 / 124 (1.61%)	0 / 123 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	2 / 2	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
encephalitis viral
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 244 (0.00%)	1 / 124 (0.81%)	0 / 123 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
peritonsillitis
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 244 (0.00%)	1 / 124 (0.81%)	0 / 123 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
tonsillitis
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 244 (0.00%)	0 / 124 (0.00%)	0 / 123 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo	1mg Baricitinib	2mg Baricitinib	4mg Baricitinib
Total subjects affected by non serious adverse events
subjects affected / exposed	34 / 244 (13.93%)	23 / 124 (18.55%)	27 / 123 (21.95%)	29 / 123 (23.58%)
Investigations
blood creatine phosphokinase increased
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	1 / 244 (0.41%)	4 / 124 (3.23%)	1 / 123 (0.81%)	7 / 123 (5.69%)
occurrences all number	1	4	1	7
Nervous system disorders
headache
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	5 / 244 (2.05%)	6 / 124 (4.84%)	9 / 123 (7.32%)	11 / 123 (8.94%)
occurrences all number	8	6	9	14
Infections and infestations
herpes simplex
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	2 / 244 (0.82%)	2 / 124 (1.61%)	7 / 123 (5.69%)	3 / 123 (2.44%)
occurrences all number	3	2	7	3
nasopharyngitis
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	30 / 244 (12.30%)	13 / 124 (10.48%)	16 / 123 (13.01%)	10 / 123 (8.13%)
occurrences all number	33	13	16	12

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib in Patients with Moderate to Severe Atopic Dermatitis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 with a ≥ 2 Point Improvement (Placebo, 2mg and 4 mg Baricitinib)

Primary: Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 with a ≥ 2 Point Improvement (Placebo, 2mg and 4 mg Baricitinib)

Secondary: Percentage of Participants Achieving IGA of 0 or 1 with a ≥ 2 Point Improvement (Placebo, 1mg Baricitinib)

Secondary: Percentage of Participants Achieving IGA of 0 or 1 with a ≥ 2 Point Improvement (Placebo, 1mg Baricitinib)

Secondary: Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75)

Secondary: Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75)

Secondary: Percentage of Participants Achieving EASI90

Secondary: Percentage of Participants Achieving EASI90

Secondary: Percent Change from Baseline (PFCB) on EASI Score

Secondary: Percent Change from Baseline (PFCB) on EASI Score

Secondary: Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75)

Secondary: Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75)

Secondary: Percentage of Participants Achieving a 4-Point Improvement on the Itch Numeric Rating Scale (NRS)

Secondary: Percentage of Participants Achieving a 4-Point Improvement on the Itch Numeric Rating Scale (NRS)

Secondary: Change from Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS)

Secondary: Change from Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS)

Secondary: Change from Baseline in Skin Pain NRS

Secondary: Change from Baseline in Skin Pain NRS

Secondary: Percentage of Participants Achieving EASI50

Secondary: Percentage of Participants Achieving EASI50

Secondary: Percentage of Participants Achieving IGA of 0

Secondary: Percentage of Participants Achieving IGA of 0

Secondary: Change from Baseline in SCORing Atopic Dermatitis (SCORAD)

Secondary: Change from Baseline in SCORing Atopic Dermatitis (SCORAD)

Secondary: Percentage of Participants Achieving SCORAD90

Secondary: Percentage of Participants Achieving SCORAD90

Secondary: Change from Baseline in Body Surface Area (BSA) Affected

Secondary: Change from Baseline in Body Surface Area (BSA) Affected

Secondary: Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment

Secondary: Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment

Secondary: Percent Change from Baseline in Itch NRS

Secondary: Percent Change from Baseline in Itch NRS

Secondary: Change from Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM)

Secondary: Change from Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM)

Secondary: Change from Baseline in the Patient Global Impression of Severity—Atopic Dermatitis (PGI-S-AD) Score

Secondary: Change from Baseline in the Patient Global Impression of Severity—Atopic Dermatitis (PGI-S-AD) Score

Secondary: Change from Baseline on the Hospital Anxiety Depression Scale (HADS)

Secondary: Change from Baseline on the Hospital Anxiety Depression Scale (HADS)

Secondary: Change from Baseline on the Dermatology Life Quality Index (DLQI)

Secondary: Change from Baseline on the Dermatology Life Quality Index (DLQI)

Secondary: Change from Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire

Secondary: Change from Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire

Secondary: Change From Baseline on the European Quality of Life–5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm

Secondary: Change From Baseline on the European Quality of Life–5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm

Secondary: Change From Baseline on the European Quality of Life–5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS)

Secondary: Change From Baseline on the European Quality of Life–5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS)

Secondary: Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement

Secondary: Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib in Patients with Moderate to Severe Atopic Dermatitis