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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 Adult Patients with Moderate to Severe Atopic Dermatitis

Summary
EudraCT number	2017-000870-12
Trial protocol	CZ DE FR DK IT
Global end of trial date	16 Aug 2019

Results information
Results version number	v1(current)
This version publication date	23 Aug 2020
First version publication date	23 Aug 2020
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-JAHL

ISRCTN number

US NCT number

NCT03334396

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 16580

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, 1 877-CTLilly,

Scientific contact

Available Mon-Fri 9 AM - 5 PM EST, Eli Lilly, 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

16 Aug 2019

Is this the analysis of the primary completion data?

Yes

Primary completion date

06 Dec 2018

Global end of trial reached?

Yes

Global end of trial date

16 Aug 2019

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 was conducted.

Background therapy

Evidence for comparator

Actual start date of recruitment

23 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

Japan: 111

Country: Number of subjects enrolled

Taiwan: 63

Country: Number of subjects enrolled

Italy: 44

Country: Number of subjects enrolled

Mexico: 73

Country: Number of subjects enrolled

India: 46

Country: Number of subjects enrolled

Russian Federation: 30

Country: Number of subjects enrolled

Czech Republic: 76

Country: Number of subjects enrolled

France: 39

Country: Number of subjects enrolled

Germany: 178

Worldwide total number of subjects

660

EEA total number of subjects

337

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)

643

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, EU#: 2017-000873-35

Screening details

No Text

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.

1 mg Baricitinib

Arm description

1 mg Baricitinib administered orally once daily.

Arm type

Experimental

Investigational medicinal product name

1 mg Baricitinib

Investigational medicinal product code

LY3009104

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

1 mg Baricitinib administered orally once daily.

2 mg Baricitinib

Arm description

2 mg Baricitinib administered orally once daily.

Arm type

Experimental

Investigational medicinal product name

2 mg Baricitinib

Investigational medicinal product code

LY3009104

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

2 mg Baricitinib administered orally once daily.

4 mg Baricitinib

Arm description

4 mg Baricitinib administered orally once daily.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

4 mg Baricitinib administered orally once daily.

Placebo Maximum Extended Enrollment (MEE)

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.

1 mg Baricitinib MEE

Arm description

1 mg Baricitinib administered orally once daily.

Arm type

Experimental

Investigational medicinal product name

1 mg Baricitinib

Investigational medicinal product code

LY3009104

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

1 mg Baricitinib administered orally once daily.

2 mg Baricitinib MEE

Arm description

2 mg Baricitinib administered orally once daily.

Arm type

Experimental

Investigational medicinal product name

2 mg Baricitinib

Investigational medicinal product code

LY3009104

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

2 mg Baricitinib administered orally once daily.

4 mg Baricitinib MEE

Arm description

4 mg Baricitinib administered orally once daily.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

4 mg Baricitinib administered orally once daily.

Number of subjects in period 1	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib	Placebo Maximum Extended Enrollment (MEE)	1 mg Baricitinib MEE	2 mg Baricitinib MEE	4 mg Baricitinib MEE
Started	249	127	123	125	15	5	8	8
Received at Least One Dose of Study Drug	249	127	123	125	15	5	8	8
Completed	226	116	113	120	12	4	5	7
Not completed	23	11	10	5	3	1	3	1
Ineligible	-	1	-	-	-	-	-	-
Physician decision	1	-	-	-	-	-	-	-
Consent withdrawn by subject	-	-	-	-	2	1	2	-
Adverse event, non-fatal	1	-	1	-	-	-	-	-
Started new job	1	-	-	-	-	-	-	-
Pregnancy	-	1	-	-	-	-	-	-
Lost to follow-up	-	-	1	-	-	-	1	-
Lack of efficacy	10	4	1	3	1	-	-	1
Withdrawal by subject	10	5	7	2	-	-	-	-

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Placebo administered orally once daily.

Reporting group title

1 mg Baricitinib

Reporting group description

1 mg Baricitinib administered orally once daily.

Reporting group title

2 mg Baricitinib

Reporting group description

2 mg Baricitinib administered orally once daily.

Reporting group title

4 mg Baricitinib

Reporting group description

4 mg Baricitinib administered orally once daily.

Reporting group title

Placebo Maximum Extended Enrollment (MEE)

Reporting group description

Placebo administered orally once daily.

Reporting group title

1 mg Baricitinib MEE

Reporting group description

1 mg Baricitinib administered orally once daily.

Reporting group title

2 mg Baricitinib MEE

Reporting group description

2 mg Baricitinib administered orally once daily.

Reporting group title

4 mg Baricitinib MEE

Reporting group description

4 mg Baricitinib administered orally once daily.

Reporting group values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib	Placebo Maximum Extended Enrollment (MEE)	1 mg Baricitinib MEE	2 mg Baricitinib MEE	4 mg Baricitinib MEE	Total
Number of subjects	249	127	123	125	15	5	8	8	660
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0	0
Adults (18-64 years)	242	127	118	121	15	5	7	8	643
From 65-84 years	7	0	5	4	0	0	1	0	17
85 years and over	0	0	0	0	0	0	0	0	0
Gender categorical
Units: Subjects
Female	101	49	41	42	6	2	0	2	243
Male	148	78	82	83	9	3	8	6	417
Race
Units: Subjects
American Indian or Alaska Native	14	7	7	2	0	0	0	0	30
Asian	73	40	35	41	15	5	8	8	225
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0
Black or African American	0	0	1	1	0	0	0	0	2
White	147	74	75	70	0	0	0	0	366
More than one race	13	6	5	10	0	0	0	0	34
Unknown or Not Reported	2	0	0	1	0	0	0	0	3
Region of Enrollment
Units: Subjects
Czechia	36	11	11	18	0	0	0	0	76
Japan	45	23	21	22	0	0	0	0	111
Taiwan	25	13	13	12	0	0	0	0	63
Italy	17	8	6	13	0	0	0	0	44
Mexico	32	15	17	9	0	0	0	0	73
France	15	4	13	7	0	0	0	0	39
Germany	67	44	37	30	0	0	0	0	178
India	1	2	1	6	15	5	8	8	46
Russia	11	7	4	8	0	0	0	0	30

End points

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Reporting group title

Placebo

Reporting group description

Placebo administered orally once daily.

Reporting group title

1 mg Baricitinib

Reporting group description

1 mg Baricitinib administered orally once daily.

Reporting group title

2 mg Baricitinib

Reporting group description

2 mg Baricitinib administered orally once daily.

Reporting group title

4 mg Baricitinib

Reporting group description

4 mg Baricitinib administered orally once daily.

Reporting group title

Placebo Maximum Extended Enrollment (MEE)

Reporting group description

Placebo administered orally once daily.

Reporting group title

1 mg Baricitinib MEE

Reporting group description

1 mg Baricitinib administered orally once daily.

Reporting group title

2 mg Baricitinib MEE

Reporting group description

2 mg Baricitinib administered orally once daily.

Reporting group title

4 mg Baricitinib MEE

Reporting group description

4 mg Baricitinib administered orally once daily.

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

End point description

The IGA measures the investigator's global assessment of the participant's 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(APD): All participants randomized to placebo, 2 mg, or 4 mg 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. A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	249	123	125
Units: percentage of participants
number (not applicable)	4.8	11.4	16.8

IGA of 0 or 1: 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

372

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.02

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.61

Confidence interval

level

95%

sides

2-sided

lower limit

1.17

upper limit

5.84

IGA of 0 or 1: 4 mg Baricitinib

Comparison groups

4 mg Baricitinib v Placebo

Number of subjects included in analysis

374

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.1

Confidence interval

level

95%

sides

2-sided

lower limit

1.93

upper limit

8.7

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

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End point title

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

End point description

The IGA measures the investigator's global assessment of the participant's 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. Analysis Population Description: All participants randomized to placebo or 1 mg 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. A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib
Number of subjects analysed	249	127
Units: percentage of participants
number (not applicable)	4.8	11.8

IGA of 0 or 1 - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.014

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.72

Confidence interval

level

95%

sides

2-sided

lower limit

1.23

upper limit

6.01

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) ^[3]

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/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 EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score. Analysis Population Description: All randomized participants.

End point type

Secondary

End point timeframe

16 Weeks

Notes
[3] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	249	127	123	125
Units: percentage of participants
number (not applicable)	8.8	17.3	18.7	24.8

EASI75 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.032

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.03

Confidence interval

level

95%

sides

2-sided

lower limit

1.06

upper limit

3.88

EASI75 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

372

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.46

Confidence interval

level

95%

sides

2-sided

lower limit

1.29

upper limit

4.67

EASI75 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

374

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.72

Confidence interval

level

95%

sides

2-sided

lower limit

2.01

upper limit

6.89

Secondary: Percentage of Participants Achieving EASI90

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End point title

Percentage of Participants Achieving EASI90 ^[4]

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/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 EASI90 is defined as a ≥ 90% improvement from baseline in the EASI score. Analysis Population Description : All randomized participants.

End point type

Secondary

End point timeframe

16 Weeks

Notes
[4] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	249	127	123	125
Units: percentage of participants
number (not applicable)	4.8	8.7	10.6	16.0

EASI90 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.21

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.73

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

4.05

EASI90 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

372

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.029

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.5

Confidence interval

level

95%

sides

2-sided

lower limit

1.1

upper limit

5.7

EASI90 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

374

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.13

Confidence interval

level

95%

sides

2-sided

lower limit

1.91

upper limit

8.91

Secondary: Percent Change From Baseline (PCFB) in EASI Score

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End point title

Percent Change From Baseline (PCFB) in EASI Score ^[5]

End point description

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 was 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 Analysis Population Description: All randomized participants who had Week 16 EASI data.

Notes
[5] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	71	52	52	70
Units: percentage of participants
least squares mean (standard error)	-34.82 ( 3.64 )	-48.22 ( 4.52 )	51.89 ( 4.29 )	-59.36 ( 3.84 )

PCFB EASI - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

123

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.021

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-13.4

Confidence interval

level

95%

sides

2-sided

lower limit

-24.77

upper limit

-2.03

Variability estimate

Standard error of the mean

Dispersion value

5.78

PCFB EASI - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

123

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-17.07

Confidence interval

level

95%

sides

2-sided

lower limit

-28.05

upper limit

-6.01

Variability estimate

Standard error of the mean

Dispersion value

5.57

PCFB EASI - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-24.54

Confidence interval

level

95%

sides

2-sided

lower limit

-34.84

upper limit

-14.24

Variability estimate

Standard error of the mean

Dispersion value

5.23

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) ^[6]

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 visual analog scale (VAS) where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a 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. Analysis Population Description: All randomized participants.

End point type

Secondary

End point timeframe

16 Weeks

Notes
[6] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	249	127	123	125
Units: percentage of participants
number (not applicable)	1.2	5.5	7.3	10.4

SCORAD 75 - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.025

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.28

Confidence interval

level

95%

sides

2-sided

lower limit

1.2

upper limit

15.24

SCORAD 75 - 2 mg Baricitinib

Comparison groups

2 mg Baricitinib v Placebo

Number of subjects included in analysis

372

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

6.14

Confidence interval

level

95%

sides

2-sided

lower limit

1.79

upper limit

20.99

SCORAD 75 - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

374

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

8.76

Confidence interval

level

95%

sides

2-sided

lower limit

2.68

upper limit

28.58

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

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End point title

Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS) ^[7]

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 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. Analysis Population Description: All randomized participants with a Baseline Itch NRS score >=4

End point type

Secondary

End point timeframe

16 Weeks

Notes
[7] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	222	105	100	107
Units: percentage of participants
number (not applicable)	7.2	10.5	12.0	21.5

Itch NRS - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

327

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.246

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

3.56

Itch NRS - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

322

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.169

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.73

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

3.77

Itch NRS - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

329

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.62

Confidence interval

level

95%

sides

2-sided

lower limit

1.82

upper limit

7.18

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

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End point title

Change From Baseline (CFB) in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS) ^[8]

End point description

The 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 adjustments made for 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. Analysis Population Description: All randomized participants with Week 16 ADSS Item 2 (frequency of waking) data.

End point type

Secondary

End point timeframe

Baseline, 16 Weeks

Notes
[8] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	68	52	50	50
Units: units on a scale
least squares mean (standard error)	-0.84 ( 0.15 )	-1.21 ( 0.18 )	-1.04 ( 0.17 )	-1.42 ( 0.16 )

CFB ADSS - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.103

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.37

Confidence interval

level

95%

sides

2-sided

lower limit

-0.82

upper limit

0.08

CFB ADSS - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.352

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.21

Confidence interval

level

95%

sides

2-sided

lower limit

-0.65

upper limit

0.23

CFB ADSS - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.58

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

-0.17

Secondary: Change from Baseline (CFB) in the Skin Pain Numeric Rating Scale (NRS)

Top of page

End point title

Change from Baseline (CFB) in the Skin Pain Numeric Rating Scale (NRS) ^[9]

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

End point type

Secondary

End point timeframe

Baseline, 16 Weeks

Notes
[9] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	68	52	50	68
Units: units on a scale
least squares mean (standard error)	-0.84 ( 0.24 )	-1.92 ( 0.30 )	-1.58 ( 0.29 )	-1.93 ( 0.26 )

CFB Skin Pain NRS - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.005

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.08

Confidence interval

level

95%

sides

2-sided

lower limit

-1.84

upper limit

-0.32

CFB Skin Pain NRS - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.051

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.74

Confidence interval

level

95%

sides

2-sided

lower limit

-1.48

upper limit

CFB Skin Pain NRS - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.09

Confidence interval

level

95%

sides

2-sided

lower limit

-1.79

upper limit

-0.39

Secondary: Percentage of Participants Achieving EASI50

Top of page

End point title

Percentage of Participants Achieving EASI50 ^[10]

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 (erythema, edema/papulation, excoriation, and 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 was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI50 is defined as a ≥ 50% improvement from baseline in EASI score. Analysis Population Description: All randomized participants.

End point type

Secondary

End point timeframe

16 Weeks

Notes
[10] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	249	127	123	125
Units: percentage of participants
number (not applicable)	15.3	26.0	30.1	41.6

EASI50 - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.019

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.9

Confidence interval

level

95%

sides

2-sided

lower limit

1.11

upper limit

3.25

EASI50 - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

372

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Mean difference (final values)

Point estimate

2.44

Confidence interval

level

95%

sides

2-sided

lower limit

1.44

upper limit

4.14

EASI50 - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

374

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Mean difference (final values)

Point estimate

4.18

Confidence interval

level

95%

sides

2-sided

lower limit

2.51

upper limit

6.96

Secondary: Percentage of Participants Achieving IGA of 0

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End point title

Percentage of Participants Achieving IGA of 0 ^[11]

End point description

The IGA measures the investigator's global assessment of the patient's 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. Analysis Population Description: All randomized participants.

End point type

Secondary

End point timeframe

16 Weeks

Notes
[11] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	249	127	123	125
Units: percentage of participants
number (not applicable)	0.8	1.6	2.4	1.6

IGA of 0 - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.424

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.37

upper limit

10.63

IGA of 0 - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

372

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.182

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

13.75

IGA of 0 - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

374

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.441

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.36

upper limit

10.41

Secondary: Change from Baseline (CFB) in SCORAD

Top of page

End point title

Change from Baseline (CFB) in SCORAD ^[12]

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 a 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 and baseline-by-visit-interaction as fixed continuous effects.

End point type

Secondary

End point timeframe

Baseline, 16 Weeks Analysis Population Description: All randomized participants with Week 16 SCORAD data.

Notes
[12] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	71	52	52	70
Units: units on scale
least squares mean (standard error)	-13.51 ( 2.00 )	-18.85 ( 2.48 )	-21.47 ( 2.36 )	-28.30 ( 2.10 )

CFB SCORAD - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

123

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.093

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-5.34

Confidence interval

level

95%

sides

2-sided

lower limit

-11.57

upper limit

0.9

Variability estimate

Standard error of the mean

Dispersion value

3.17

CFB SCORAD - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

123

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.01

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-7.97

Confidence interval

level

95%

sides

2-sided

lower limit

-14.01

upper limit

-1.92

Variability estimate

Standard error of the mean

Dispersion value

3.07

CFB SCORAD - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-14.79

Confidence interval

level

95%

sides

2-sided

lower limit

-20.46

upper limit

-9.13

Variability estimate

Standard error of the mean

Dispersion value

2.88

Secondary: Percentage of Participants Achieving SCORAD90

Top of page

End point title

Percentage of Participants Achieving SCORAD90 ^[13]

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 in the last 72 hours on visual analogue scales (VAS) of 0 to 10 where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a 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 is defined as having ≥ 90% improvement in SCORAD from baseline. Analysis Population Description: All randomized participants.

End point type

Secondary

End point timeframe

16 Weeks

Notes
[13] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	249	127	123	125
Units: percentage of participants
number (not applicable)	0.8	0.8	2.4	2.4

SCORAD90 - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.874

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.17

Confidence interval

level

95%

sides

2-sided

lower limit

0.17

upper limit

7.77

SCORAD90 - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

372

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.176

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.62

upper limit

13.36

SCORAD90 - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

374

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.201

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.59

upper limit

12.65

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

Top of page

End point title

Change From Baseline (CFB) in Body Surface Area (BSA) Affected ^[14]

End point description

Body surface area (BSA) 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 Analysis Population Description: All randomized participants with Week 16 BSA.

Notes
[14] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	71	52	52	70
Units: units on a scale
least squares mean (standard error)	-14.80 ( 1.82 )	-20.79 ( 2.26 )	-20.14 ( 2.16 )	-25.96 ( 1.93 )

CFB BSA - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

123

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.039

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-5.99

Confidence interval

level

95%

sides

2-sided

lower limit

-11.67

upper limit

-0.31

Variability estimate

Standard error of the mean

Dispersion value

2.88

CFB BSA - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

123

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.058

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-5.34

Confidence interval

level

95%

sides

2-sided

lower limit

-10.86

upper limit

0.18

Variability estimate

Standard error of the mean

Dispersion value

2.8

CFB BSA - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-11.16

Confidence interval

level

95%

sides

2-sided

lower limit

-16.33

upper limit

-5.98

Variability estimate

Standard error of the mean

Dispersion value

2.63

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 ^[15]

End point description

Percentage of participants developing skin infections requiring antibiotic treatment. Analysis Population Description: All randomized participants.

End point type

Secondary

End point timeframe

16 Weeks

Notes
[15] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	249	127	123	125
Units: percentage of partcipants
number (not applicable)	4.4	0.8	4.9	3.2

Skin Infections - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.067

Method

Fisher exact

Confidence interval

Skin Infections - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

372

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.799

Method

Fisher exact

Confidence interval

Skin Infections - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

374

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.782

Method

Fisher exact

Confidence interval

Secondary: Percent Change From Baseline (PCFB) in Itch NRS

Top of page

End point title

Percent Change From Baseline (PCFB) in Itch NRS ^[16]

End point description

The Itch 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 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. 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. Analysis Population Description: All randomized participants with Week 16 Itch NRS data.

End point type

Secondary

End point timeframe

Baseline, 16 Weeks

Notes
[16] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	68	52	50	68
Units: units on a scale
least squares mean (standard error)	-12.04 ( 4.65 )	-31.30 ( 5.70 )	-29.43 ( 5.45 )	-36.55 ( 4.88 )

PCFB Itch NRS - 1 mg Baricitinib

Comparison groups

1 mg Baricitinib v Placebo

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.009

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-19.25

Confidence interval

level

95%

sides

2-sided

lower limit

-33.69

upper limit

-4.81

Variability estimate

Standard error of the mean

Dispersion value

7.33

PCFB Itch NRS - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.015

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-17.39

Confidence interval

level

95%

sides

2-sided

lower limit

-31.43

upper limit

-3.35

Variability estimate

Standard error of the mean

Dispersion value

7.13

PCFB Itch NRS - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-24.5

Confidence interval

level

95%

sides

2-sided

lower limit

-37.71

upper limit

-11.3

Variability estimate

Standard error of the mean

Dispersion value

6.71

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

Top of page

End point title

Change From Baseline (CFB) in the Total Score of the Patient Oriented Eczema Measure (POEM) ^[17]

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. 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. Analysis Population Description: All randomized participants with Week 16 POEM data.

End point type

Secondary

End point timeframe

Baseline, 16 Weeks

Notes
[17] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	72	53	52	70
Units: units on a scale
least squares mean (standard error)	-2.68 ( 0.76 )	-5.32 ( 0.93 )	-6.26 ( 0.91 )	-7.84 ( 0.80 )

CFB POEM - 1 mg Baricitinib

Comparison groups

1 mg Baricitinib v Placebo

Number of subjects included in analysis

125

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.028

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-2.63

Confidence interval

level

95%

sides

2-sided

lower limit

-4.98

upper limit

-0.29

Variability estimate

Standard error of the mean

Dispersion value

1.19

CFB POEM - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-3.58

Confidence interval

level

95%

sides

2-sided

lower limit

-5.89

upper limit

-1.27

Variability estimate

Standard error of the mean

Dispersion value

1.17

CFB POEM - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-5.16

Confidence interval

level

95%

sides

2-sided

lower limit

-7.33

upper limit

-2.99

Variability estimate

Standard error of the mean

Dispersion value

1.1

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

Top of page

End point title

Change from Baseline (CFB) in the Patient Global Impression of Severity—Atopic Dermatitis (PGI-S-AD) Score ^[18]

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 were used for the PGI-S-AD, i.e.,"(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. Analysis Population Description: All randomized participants with Week 16 PGI-S-AD score.

End point type

Secondary

End point timeframe

Baseline, 16 Weeks

Notes
[18] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	68	52	50	68
Units: units on a scale
least squares mean (standard error)	-0.31 ( 0.09 )	-0.58 ( 0.12 )	-0.58 ( 0.11 )	-0.77 ( 0.10 )

CFB PGI-S-AD - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.069

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.27

Confidence interval

level

95%

sides

2-sided

lower limit

-0.56

upper limit

0.02

Variability estimate

Standard error of the mean

Dispersion value

0.15

CFB PGI-S-AD - 2mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.066

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.27

Confidence interval

level

95%

sides

2-sided

lower limit

-0.56

upper limit

0.02

Variability estimate

Standard error of the mean

Dispersion value

0.15

CFB PGI-S-AD - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.46

Confidence interval

level

95%

sides

2-sided

lower limit

-0.73

upper limit

-0.19

Variability estimate

Standard error of the mean

Dispersion value

0.14

Secondary: Change From Baseline (CFB) on the Hospital Anxiety and Depression Scale (HADS)

Top of page

End point title

Change From Baseline (CFB) on the Hospital Anxiety and Depression Scale (HADS) ^[19]

End point description

The HADS is a participant-rated instrument used to assess both anxiety and depression. This instrument consists of 14 item 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. 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. Analysis Population Description: All randomized participants with Week 16 HADS data.

End point type

Secondary

End point timeframe

Baseline, 16 Weeks

Notes
[19] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	71	51	52	70
Units: units on a scale
least squares mean (standard error)
Anxiety	-0.90 ( 0.28 )	-1.35 ( 0.34 )	-1.83 ( 0.33 )	-2.05 ( 0.30 )
Depression	-0.37 ( 0.27 )	-1.04 ( 0.34 )	-1.40 ( 0.32 )	-1.50 ( 0.29 )

CFB HADS Anxiety - 1 mg Baricitinib

Statistical analysis description

HADS Anxiety

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.305

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.45

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

0.41

Variability estimate

Standard error of the mean

Dispersion value

0.43

CFB HADS Anxiety - 2 mg Baricitinib

Statistical analysis description

HADS Anxiety

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

123

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.029

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.93

Confidence interval

level

95%

sides

2-sided

lower limit

-1.77

upper limit

-0.1

Variability estimate

Standard error of the mean

Dispersion value

0.42

CFB HADS Anxiety - 4 mg Baricitinib

Statistical analysis description

HADS Anxiety

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.15

Confidence interval

level

95%

sides

2-sided

lower limit

-1.93

upper limit

-0.36

Variability estimate

Standard error of the mean

Dispersion value

0.4

CFB HADS Depression - 1 mg Baricitinib

Statistical analysis description

HADS Depression

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.113

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.68

Confidence interval

level

95%

sides

2-sided

lower limit

-1.51

upper limit

0.16

Variability estimate

Standard error of the mean

Dispersion value

0.43

CFB HADS Depression - 2 mg Baricitinib

Statistical analysis description

HADS Depression

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

123

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.014

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.03

Confidence interval

level

95%

sides

2-sided

lower limit

-1.85

upper limit

-0.22

Variability estimate

Standard error of the mean

Dispersion value

0.42

CFB HADS Depression - 4 mg Baricitinib

Statistical analysis description

HADS Depression

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.14

Confidence interval

level

95%

sides

2-sided

lower limit

-1.91

upper limit

-0.37

Variability estimate

Standard error of the mean

Dispersion value

0.39

Secondary: Change From Baseline (CFB) in the Dermatology Life Quality Index (DLQI)

Top of page

End point title

Change From Baseline (CFB) in the Dermatology Life Quality Index (DLQI) ^[20]

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. 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. Analysis Population Description: All randomized participants with Week 16 DLQI data.

End point type

Secondary

End point timeframe

Baseline, 16 Weeks

Notes
[20] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	71	52	52	70
Units: units on a scale
least squares mean (standard error)	-2.46 ( 0.57 )	-4.64 ( 0.70 )	-4.30 ( 0.68 )	-6.76 ( 0.60 )

CFB DLQI - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

123

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.015

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-2.17

Confidence interval

level

95%

sides

2-sided

lower limit

-3.92

upper limit

-0.42

Variability estimate

Standard error of the mean

Dispersion value

0.89

CFB DLQI - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

123

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.036

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.84

Confidence interval

level

95%

sides

2-sided

lower limit

-3.56

upper limit

-0.12

Variability estimate

Standard error of the mean

Dispersion value

0.87

CFB DLQI - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-4.3

Confidence interval

level

95%

sides

2-sided

lower limit

-5.91

upper limit

-2.69

Variability estimate

Standard error of the mean

Dispersion value

0.82

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

Top of page

End point title

Change from Baseline (CFB) on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire ^[21]

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 into 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. LS Mean 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. Analysis Population Description: All randomized participants with Week 16 WPAI-AD data.

End point type

Secondary

End point timeframe

Baseline, 16 Weeks

Notes
[21] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	70	51	52	70
Units: units on a scale
least squares mean (standard error)
Absenteeism (48, 30, 27, 40)	-0.49 ( 1.68 )	4.54 ( 2.15 )	-0.84 ( 2.23 )	-3.89 ( 1.88 )
Presenteeism( 48, 30, 27, 40)	-2.98 ( 2.60 )	-9.75 ( 3.37 )	-11.53 ( 3.44 )	-15.57 ( 2.95 )
Work Productivity Loss ( 48, 30, 27, 39)	-2.57 ( 2.60 )	-11.23 ( 3.75 )	-9.06 ( 3.83 )	-13.85 ( 3.29 )
Activity Impairment (70, 51, 52, 70)	-5.67 ( 2.16 )	-12.98 ( 2.63 )	-10.80 ( 2.57 )	-22.20 ( 2.30 )

CFB Absenteeism - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.136

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-4.05

Confidence interval

level

95%

sides

2-sided

lower limit

-9.39

upper limit

1.29

Variability estimate

Standard error of the mean

Dispersion value

2.7

CFB Absenteeism - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.898

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.35

Confidence interval

level

95%

sides

2-sided

lower limit

-5.81

upper limit

5.1

Variability estimate

Standard error of the mean

Dispersion value

2.76

CFB Absenteeism - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.174

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-3.4

Confidence interval

level

95%

sides

2-sided

lower limit

-8.32

upper limit

1.52

Variability estimate

Standard error of the mean

Dispersion value

2.49

CFB Presenteeism - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.104

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-6.86

Confidence interval

level

95%

sides

2-sided

lower limit

-15.13

upper limit

1.41

Variability estimate

Standard error of the mean

Dispersion value

4.19

CFB Presenteeism - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.045

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-8.64

Confidence interval

level

95%

sides

2-sided

lower limit

-17.09

upper limit

-0.19

Variability estimate

Standard error of the mean

Dispersion value

4.28

CFB Presenteeism - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

superiority ^[22]

P-value

= 0.002

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-12.28

Confidence interval

level

95%

sides

2-sided

lower limit

-19.97

upper limit

-4.59

Variability estimate

Standard error of the mean

Dispersion value

3.9

Notes
[22] - Presentisms

CFB Work Productivity Loss - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.066

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-8.66

Confidence interval

level

95%

sides

2-sided

lower limit

-17.89

upper limit

0.57

Variability estimate

Standard error of the mean

Dispersion value

4.67

CFB Work Productivity Loss - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.175

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-6.49

Confidence interval

level

95%

sides

2-sided

lower limit

-15.89

upper limit

2.91

Variability estimate

Standard error of the mean

Dispersion value

4.76

CFB Work Productivity Loss - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.01

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-11.28

Confidence interval

level

95%

sides

2-sided

lower limit

-19.84

upper limit

-2.72

Variability estimate

Standard error of the mean

Dispersion value

4.94

CFB Activity Impairment - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.03

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-7.31

Confidence interval

level

95%

sides

2-sided

lower limit

-13.93

upper limit

-0.7

Variability estimate

Standard error of the mean

Dispersion value

3.36

CFB Activity Impairment - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.122

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-5.13

Confidence interval

level

95%

sides

2-sided

lower limit

-11.65

upper limit

1.39

Variability estimate

Standard error of the mean

Dispersion value

3.31

CFB Activity Impairment - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-16.52

Confidence interval

level

95%

sides

2-sided

lower limit

-22.64

upper limit

-10.41

Variability estimate

Standard error of the mean

Dispersion value

3.11

Secondary: Change From Baseline (CFB) 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 (CFB) on the European Quality of Life–5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm ^[23]

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. Responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, scores range from -0.594 to 1, and the United States (US) algorithm, scores range from -0.109 to 1. Higher scores indicate better health state. LS Mean 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. Analysis Population Description: All randomized participants with Week 16 EQ-5D-5L health state index US and UK data.

End point type

Secondary

End point timeframe

Baseline, 16 Weeks

Notes
[23] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	70	51	52	70
Units: units on a scale
least squares mean (standard error)
Health State Index Score US (70, 51, 52, 70)	0.01 ( 0.01 )	0.05 ( 0.02 )	0.05 ( 0.02 )	0.09 ( 0.01 )
Health State Index Score UK (70, 51, 52, 70)	0.01 ( 0.02 )	0.07 ( 0.02 )	0.07 ( 0.02 )	0.13 ( 0.02 )

CFB Health State Index US - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.061

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.04

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

0.08

Variability estimate

Standard error of the mean

Dispersion value

0.02

CFB Health State Index US - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.06

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.04

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

0.08

Variability estimate

Standard error of the mean

Dispersion value

0.02

CFB Health State Index US - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.08

Confidence interval

level

95%

sides

2-sided

lower limit

0.04

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 1 mg Baricitinib

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.046

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.06

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

0.11

Variability estimate

Standard error of the mean

Dispersion value

0.03

CFB Health State Index UK - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.059

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

0.11

Variability estimate

Standard error of the mean

Dispersion value

0.03

CFB Health State Index UK - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.06

upper limit

0.16

Variability estimate

Standard error of the mean

Dispersion value

0.03

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

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End point title

Change From Baseline (CFB) on the European Quality of Life–5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS) ^[24]

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. LS Mean 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. Analysis Population Description: All randomized participants with Week 16 EQ-5D-5L VAS data.

End point type

Secondary

End point timeframe

Baseline, 16 Weeks

Notes
[24] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	70	51	52	70
Units: millimeters
least squares mean (standard error)	2.00 ( 2.04 )	4.97 ( 2.53 )	3.35 ( 2.41 )	9.05 ( 2.17 )

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

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.356

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

2.97

Confidence interval

level

95%

sides

2-sided

lower limit

-3.36

upper limit

9.3

Variability estimate

Standard error of the mean

Dispersion value

3.21

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

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.688

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.34

Confidence interval

level

95%

sides

2-sided

lower limit

-4.81

upper limit

7.5

Variability estimate

Standard error of the mean

Dispersion value

3.13

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

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.017

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

7.05

Confidence interval

level

95%

sides

2-sided

lower limit

1.25

upper limit

12.86

Variability estimate

Standard error of the mean

Dispersion value

2.95

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

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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 ^[25]

End point description

End point type

Secondary

End point timeframe

Week 4

Notes
[25] - 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: A Maximum Extended Enrollment (MEE) cohort is implemented in countries to meet regulatory requirements for submission. Data from any MEE country-specific cohort will not be incorporated into the analysis of the global study cohort.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	249	127	123	125
Units: Percentage of Participants
number (not applicable)	2.4	3.1	8.9	10.4

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

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.603

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.38

Confidence interval

level

95%

sides

2-sided

lower limit

0.41

upper limit

4.71

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

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

372

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.08

Confidence interval

level

95%

sides

2-sided

lower limit

1.5

upper limit

11.12

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

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

374

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.72

Confidence interval

level

95%

sides

2-sided

lower limit

1.78

upper limit

12.35

Adverse events

Top of page

Timeframe for reporting adverse events

Baseline Up to 20 weeks

Adverse event reporting additional description

I4V-MC-JAHL

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.1

Reporting group title

Placebo

Reporting group description

Reporting group title

1 mg Baricitinib

Reporting group description

Reporting group title

2 mg Baricitinib

Reporting group description

Reporting group title

4 mg Baricitinib

Reporting group description

Reporting group title

Placebo Maximum Extended Enrollment (MEE)

Reporting group description

Reporting group title

1 mg Baricitinib MEE

Reporting group description

Reporting group title

2 mg Baricitinib MEE

Reporting group description

Reporting group title

4 mg Baricitinib MEE

Reporting group description

Serious adverse events	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib	Placebo Maximum Extended Enrollment (MEE)	1 mg Baricitinib MEE	2 mg Baricitinib MEE	4 mg Baricitinib MEE
Total subjects affected by serious adverse events
subjects affected / exposed	6 / 249 (2.41%)	1 / 127 (0.79%)	0 / 123 (0.00%)	2 / 125 (1.60%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
breast cancer
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	1 / 249 (0.40%)	0 / 127 (0.00%)	0 / 123 (0.00%)	0 / 125 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
papillary thyroid cancer
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	1 / 249 (0.40%)	0 / 127 (0.00%)	0 / 123 (0.00%)	0 / 125 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
alcohol poisoning
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 249 (0.00%)	0 / 127 (0.00%)	0 / 123 (0.00%)	1 / 125 (0.80%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
clavicle fracture
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	1 / 249 (0.40%)	0 / 127 (0.00%)	0 / 123 (0.00%)	0 / 125 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
rib fracture
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	1 / 249 (0.40%)	0 / 127 (0.00%)	0 / 123 (0.00%)	0 / 125 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
dermatitis atopic
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	2 / 249 (0.80%)	1 / 127 (0.79%)	0 / 123 (0.00%)	1 / 125 (0.80%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 2	1 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
suicide attempt
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	1 / 249 (0.40%)	0 / 127 (0.00%)	0 / 123 (0.00%)	0 / 125 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib	Placebo Maximum Extended Enrollment (MEE)	1 mg Baricitinib MEE	2 mg Baricitinib MEE	4 mg Baricitinib MEE
Total subjects affected by non serious adverse events
subjects affected / exposed	55 / 249 (22.09%)	37 / 127 (29.13%)	34 / 123 (27.64%)	29 / 125 (23.20%)	3 / 15 (20.00%)	1 / 5 (20.00%)	2 / 8 (25.00%)	3 / 8 (37.50%)
Investigations
weight decreased
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 249 (0.00%)	0 / 127 (0.00%)	0 / 123 (0.00%)	0 / 125 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Nervous system disorders
headache
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	16 / 249 (6.43%)	7 / 127 (5.51%)	14 / 123 (11.38%)	10 / 125 (8.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)
occurrences all number	17	8	15	11	0	0	0	0
Blood and lymphatic system disorders
anaemia
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	1 / 249 (0.40%)	0 / 127 (0.00%)	0 / 123 (0.00%)	1 / 125 (0.80%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	1	1	0	0	0
leukopenia
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 249 (0.00%)	0 / 127 (0.00%)	0 / 123 (0.00%)	0 / 125 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
lymphopenia
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 249 (0.00%)	0 / 127 (0.00%)	1 / 123 (0.81%)	1 / 125 (0.80%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	1	1	0	0	0
neutropenia
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	1 / 249 (0.40%)	0 / 127 (0.00%)	0 / 123 (0.00%)	0 / 125 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0
General disorders and administration site conditions
oedema
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	1 / 249 (0.40%)	0 / 127 (0.00%)	0 / 123 (0.00%)	0 / 125 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0
oedema peripheral
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	1 / 249 (0.40%)	0 / 127 (0.00%)	0 / 123 (0.00%)	0 / 125 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)
occurrences all number	1	0	0	0	0	0	0	1
pyrexia
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 249 (0.00%)	1 / 127 (0.79%)	3 / 123 (2.44%)	1 / 125 (0.80%)	0 / 15 (0.00%)	1 / 5 (20.00%)	1 / 8 (12.50%)	1 / 8 (12.50%)
occurrences all number	0	1	3	1	0	1	1	1
Gastrointestinal disorders
abdominal pain
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	1 / 249 (0.40%)	2 / 127 (1.57%)	3 / 123 (2.44%)	0 / 125 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)
occurrences all number	1	2	4	0	0	0	0	1
diarrhoea
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	7 / 249 (2.81%)	9 / 127 (7.09%)	0 / 123 (0.00%)	4 / 125 (3.20%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)
occurrences all number	8	9	0	4	1	0	0	0
nausea
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	2 / 249 (0.80%)	1 / 127 (0.79%)	1 / 123 (0.81%)	1 / 125 (0.80%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)
occurrences all number	2	1	1	1	0	0	0	1
Respiratory, thoracic and mediastinal disorders
cough
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	2 / 249 (0.80%)	0 / 127 (0.00%)	0 / 123 (0.00%)	4 / 125 (3.20%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)
occurrences all number	2	0	0	4	1	0	0	0
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	1 / 249 (0.40%)	2 / 127 (1.57%)	1 / 123 (0.81%)	0 / 125 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	2	1	0	1	0	0	0
Infections and infestations
nasopharyngitis
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	26 / 249 (10.44%)	22 / 127 (17.32%)	12 / 123 (9.76%)	12 / 125 (9.60%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)
occurrences all number	28	25	14	17	0	0	0	0
oral herpes
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 249 (0.00%)	3 / 127 (2.36%)	2 / 123 (1.63%)	2 / 125 (1.60%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	4	2	2	1	0	0	0
skin infection
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	1 / 249 (0.40%)	0 / 127 (0.00%)	1 / 123 (0.81%)	0 / 125 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)
occurrences all number	1	0	1	0	0	0	0	3
urinary tract infection
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	4 / 249 (1.61%)	1 / 127 (0.79%)	2 / 123 (1.63%)	4 / 125 (3.20%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	1 / 8 (12.50%)
occurrences all number	4	1	2	7	0	0	1	1
vulvovaginal candidiasis
alternative dictionary used: MedDRA 21.1
subjects affected / exposed ^[1]	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 41 (0.00%)	0 / 42 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly. The 2 mg Baricitinib MEE reporting group had 8 male and 0 female participants. The number of participants exposed should be zero, however the EudraCT Results Database requires a value of greater than or equal to 1 for this field. The number of participants exposed cannot be adjusted to zero for this gender specific adverse event due to a system issue.

More information

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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 Adult 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 (2 mg and 4 mg Baricitinib)

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

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

Secondary: Percentage of Participants Achieving IGA of 0 or 1 With a ≥ 2 Point Improvement (1 mg 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 (PCFB) in EASI Score

Secondary: Percent Change From Baseline (PCFB) in 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 in Itch Numeric Rating Scale (NRS)

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

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

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

Secondary: Change from Baseline (CFB) in the Skin Pain Numeric Rating Scale (NRS)

Secondary: Change from Baseline (CFB) in the Skin Pain Numeric Rating Scale (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 (CFB) in SCORAD

Secondary: Change from Baseline (CFB) in SCORAD

Secondary: Percentage of Participants Achieving SCORAD90

Secondary: Percentage of Participants Achieving SCORAD90

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

Secondary: Change From Baseline (CFB) 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 (PCFB) in Itch NRS

Secondary: Percent Change From Baseline (PCFB) in Itch NRS

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

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

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

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

Secondary: Change From Baseline (CFB) on the Hospital Anxiety and Depression Scale (HADS)

Secondary: Change From Baseline (CFB) on the Hospital Anxiety and Depression Scale (HADS)

Secondary: Change From Baseline (CFB) in the Dermatology Life Quality Index (DLQI)

Secondary: Change From Baseline (CFB) in the Dermatology Life Quality Index (DLQI)

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

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

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

Secondary: Change From Baseline (CFB) 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

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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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 Adult Patients with Moderate to Severe Atopic Dermatitis