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Clinical Trial Results:
A Phase 2b Multicenter, Randomized, Placebo-Controlled, Double-Blind Dose-Ranging Study to Evaluate ABT-494 (Upadacitinib) in Adult Subjects with Moderate to Severe Atopic Dermatitis

Summary
EudraCT number	2016-002451-21
Trial protocol	NL FI IE BE ES
Global end of trial date	31 Jan 2019

Results information
Results version number	v2(current)
This version publication date	15 Aug 2020
First version publication date	08 Feb 2020
Other versions	v1
Version creation reason	New data added to full data set Correction to study arms in safety section.

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

M16-048

ISRCTN number

US NCT number

NCT02925117

WHO universal trial number (UTN)

Sponsor organisation name

Abbvie Deutschland GmbH & Co.KG

Sponsor organisation address

AbbVie House, Vanwall Business Park, Maidenhead, Berkshire, United Kingdom, SL6-4UB

Public contact

Global Medical Services, AbbVie, 011 800-633-9110,

Scientific contact

Alvina Chu, MD, AbbVie, alvina.chu@abbvie.com

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

31 Jan 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

31 Jan 2019

Was the trial ended prematurely?

Main objective of the trial

The objective of this study was to evaluate the safety and efficacy of multiple doses of upadacitinib monotherapy versus placebo in the treatment of adults with moderate to severe atopic dermatitis (AD).

Protection of trial subjects

All subjects entering the study had to sign an informed consent that was explained to them and questions encouraged.

Background therapy

Evidence for comparator

Actual start date of recruitment

25 Oct 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 17

Country: Number of subjects enrolled

Canada: 41

Country: Number of subjects enrolled

Finland: 3

Country: Number of subjects enrolled

Germany: 3

Country: Number of subjects enrolled

Japan: 10

Country: Number of subjects enrolled

Netherlands: 17

Country: Number of subjects enrolled

Spain: 1

Country: Number of subjects enrolled

United States: 75

Worldwide total number of subjects

167

EEA total number of subjects

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)

152

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Participants were enrolled at 36 sites in 8 countries (Australia, Canada, Finland, Germany, Japan, Netherlands, Spain, and the United States [US]). The study included a 16-week double-blind treatment period (period 1) followed by a a 72-week double-blind treatment period (Period 2) for a total of 88 weeks of treatment.

Screening details

Participants were randomized in a 1:1:1:1 ratio, stratified by geographic region (US and Canada; European Union and Australia; and Japan). Participants who completed Period 1 were re-randomized at Week 16 within their original treatment group assignments to either upadacitinib or placebo in a 1:1 ratio. Rescue therapy was provided from Week 20.

Period 1 title

Period 1

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

Participants randomized to receive placebo once daily (QD) for 16 weeks in Period 1.

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

Administered orally once a day

Upadacitinib 7.5 mg

Arm description

Participants randomized to receive upadacitinib 7.5 mg once daily for 16 weeks in Period 1.

Arm type

Experimental

Investigational medicinal product name

Upadacitinib

Investigational medicinal product code

ABT-494

Other name

RINVOQ™

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

Upadacitinib 15 mg

Arm description

Participants randomized to receive upadacitinib 15 mg once daily for 16 weeks in Period 1.

Arm type

Experimental

Investigational medicinal product name

Upadacitinib

Investigational medicinal product code

ABT-494

Other name

RINVOQ™

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

Upadacitinib 30 mg

Arm description

Participants randomized to receive upadacitinib 30 mg once daily for 16 weeks in Period 1.

Arm type

Experimental

Investigational medicinal product name

Upadacitinib

Investigational medicinal product code

ABT-494

Other name

RINVOQ™

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

Number of subjects in period 1	Placebo	Upadacitinib 7.5 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Started	41	42	42	42
Received Treatment	40	42	42	42
Completed	23	31	37	39
Not completed	18	11	5	3
Consent withdrawn by subject	10	3	3	-
Adverse event, non-fatal	1	3	1	2
Other	5	4	1	1
Lost to follow-up	2	1	-	-

Period 2 title

Period 2

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo / Placebo

Arm description

Participants originally randomized to placebo were re-randomized at Week 16 to receive placebo tablets once a day for 72 weeks in Period 2.

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

Administered orally once a day

Placebo / Upadacitinib 30 mg

Arm description

Participants originally randomized to placebo were re-randomized at Week 16 to receive 30 mg upadacitinib once a day for 72 weeks in Period 2.

Arm type

Experimental

Investigational medicinal product name

Upadacitinib

Investigational medicinal product code

ABT-494

Other name

RINVOQ™

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

Upadacitinib 7.5 mg / Placebo

Arm description

Participants originally randomized to 7.5 mg upadacitinib were re-randomized at Week 16 to receive placebo tablets once a day for 72 weeks in Period 2.

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

Administered orally once a day

Upadacitinib 7.5 mg / Upadacitinib 7.5 mg

Arm description

Participants originally randomized to 7.5 mg upadacitinib were re-randomized at Week 16 to receive 7.5 mg upadacitinib once a day for 72 weeks in Period 2.

Arm type

Experimental

Investigational medicinal product name

Upadacitinib

Investigational medicinal product code

ABT-494

Other name

RINVOQ™

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

Upadacitinib 15 mg / Placebo

Arm description

Participants originally randomized to 15 mg upadacitinib were re-randomized at Week 16 to receive placebo tablets once a day for 72 weeks in Period 2.

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

Administered orally once a day

Upadacitinib 15 mg / Upadacitinib 15 mg

Arm description

Participants originally randomized to 15 mg upadacitinib were re-randomized at Week 16 to receive 15 mg upadacitinib once a day for 72 weeks in Period 2.

Arm type

Experimental

Investigational medicinal product name

Upadacitinib

Investigational medicinal product code

ABT-494

Other name

RINVOQ™

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

Upadacitinib 30 mg / Placebo

Arm description

Participants originally randomized to 30 mg upadacitinib were re-randomized at Week 16 to receive placebo tablets once a day for 72 weeks in Period 2.

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

Administered orally once a day

Upadacitinib 30 mg / Upadacitinib 30 mg

Arm description

Participants originally randomized to 30 mg upadacitinib were re-randomized at Week 16 to receive 30 mg upadacitinib once a day for 72 weeks in Period 2.

Arm type

Experimental

Investigational medicinal product name

Upadacitinib

Investigational medicinal product code

ABT-494

Other name

RINVOQ™

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

Number of subjects in period 2 ^[1]	Placebo / Placebo	Placebo / Upadacitinib 30 mg	Upadacitinib 7.5 mg / Placebo	Upadacitinib 7.5 mg / Upadacitinib 7.5 mg	Upadacitinib 15 mg / Placebo	Upadacitinib 15 mg / Upadacitinib 15 mg	Upadacitinib 30 mg / Placebo	Upadacitinib 30 mg / Upadacitinib 30 mg
Started	10	10	15	16	19	18	19	19
Received Treatment	10	10	15	16	19	18	19	19
Rescued by Upadacitinib 30 mg	8	1 ^[2]	13	12	17	12	14	4 ^[3]
Completed	8	5	9	11	13	12	11	14
Not completed	2	5	6	5	6	6	8	5
Consent withdrawn by subject	-	1	4	3	2	2	2	2
Adverse event, non-fatal	-	1	-	-	-	-	3	2
Other	1	1	1	1	3	4	3	-
Lost to follow-up	1	2	1	1	1	-	-	1

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Four participants completed Week 16 but were not re-randomized into Period 2.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant re-randomized to 30 mg upadacitinib was rescued during Period 2; 5 participants completed Period 2.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Four participants re-randomized to 30 mg upadacitinib were rescued during Period 2; 14 participants completed Period 2.

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Participants randomized to receive placebo once daily (QD) for 16 weeks in Period 1.

Reporting group title

Upadacitinib 7.5 mg

Reporting group description

Participants randomized to receive upadacitinib 7.5 mg once daily for 16 weeks in Period 1.

Reporting group title

Upadacitinib 15 mg

Reporting group description

Participants randomized to receive upadacitinib 15 mg once daily for 16 weeks in Period 1.

Reporting group title

Upadacitinib 30 mg

Reporting group description

Participants randomized to receive upadacitinib 30 mg once daily for 16 weeks in Period 1.

Reporting group values	Placebo	Upadacitinib 7.5 mg	Upadacitinib 15 mg	Upadacitinib 30 mg	Total
Number of subjects	41	42	42	42	167
Age categorical
Units: Subjects
< 40 years	25	22	25	22	94
40 - 64 years	11	16	14	17	58
≥ 65 years	5	4	3	3	15
Age continuous
Units: years
arithmetic mean (standard deviation)	39.9 ± 17.52	41.5 ± 15.36	38.5 ± 15.24	39.9 ± 15.30	-
Gender categorical
Units: Subjects
Female	17	14	12	20	63
Male	24	28	30	22	104
Race
Units: Subjects
White	28	24	21	23	96
Black or African American	6	7	10	6	29
Asian	7	9	9	13	38
American Indian/Alaska Native	0	0	1	0	1
Native Hawaiian or Other Pacific Islander	0	2	1	0	3
Ethnicity
Units: Subjects
Hispanic or Latino	0	2	2	1	5
Not Hispanic or Latino	41	40	40	41	162
Geographic Region
Units: Subjects
US/Canada	29	29	29	29	116
EU/Australia	10	11	10	10	41
Japan	2	2	3	3	10
Duration of Atopic Dermatitis Diagnosis
n = 40 in the placebo group
Units: years
arithmetic mean (standard deviation)	26.84 ± 18.76	30.44 ± 18.07	22.59 ± 15.78	24.24 ± 13.58	-
Eczema Area and Severity Index (EASI)
EASI is a tool to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected, and the severity of eczema (scored as none [0], mild [1], moderate [2], or severe [3]) for redness, thickness, scratching, and lichenification are assessed. The EASI score is the sum of the scores for each region and ranges from 0 to 72, where higher scores represent worse disease.
Units: scores on a scale
arithmetic mean (standard deviation)	32.62 ± 14.49	31.42 ± 15.76	31.40 ± 12.26	28.15 ± 11.62	-

End points

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Reporting group title

Placebo

Reporting group description

Participants randomized to receive placebo once daily (QD) for 16 weeks in Period 1.

Reporting group title

Upadacitinib 7.5 mg

Reporting group description

Participants randomized to receive upadacitinib 7.5 mg once daily for 16 weeks in Period 1.

Reporting group title

Upadacitinib 15 mg

Reporting group description

Participants randomized to receive upadacitinib 15 mg once daily for 16 weeks in Period 1.

Reporting group title

Upadacitinib 30 mg

Reporting group description

Participants randomized to receive upadacitinib 30 mg once daily for 16 weeks in Period 1.

Reporting group title

Placebo / Placebo

Reporting group description

Participants originally randomized to placebo were re-randomized at Week 16 to receive placebo tablets once a day for 72 weeks in Period 2.

Reporting group title

Placebo / Upadacitinib 30 mg

Reporting group description

Participants originally randomized to placebo were re-randomized at Week 16 to receive 30 mg upadacitinib once a day for 72 weeks in Period 2.

Reporting group title

Upadacitinib 7.5 mg / Placebo

Reporting group description

Participants originally randomized to 7.5 mg upadacitinib were re-randomized at Week 16 to receive placebo tablets once a day for 72 weeks in Period 2.

Reporting group title

Upadacitinib 7.5 mg / Upadacitinib 7.5 mg

Reporting group description

Participants originally randomized to 7.5 mg upadacitinib were re-randomized at Week 16 to receive 7.5 mg upadacitinib once a day for 72 weeks in Period 2.

Reporting group title

Upadacitinib 15 mg / Placebo

Reporting group description

Participants originally randomized to 15 mg upadacitinib were re-randomized at Week 16 to receive placebo tablets once a day for 72 weeks in Period 2.

Reporting group title

Upadacitinib 15 mg / Upadacitinib 15 mg

Reporting group description

Participants originally randomized to 15 mg upadacitinib were re-randomized at Week 16 to receive 15 mg upadacitinib once a day for 72 weeks in Period 2.

Reporting group title

Upadacitinib 30 mg / Placebo

Reporting group description

Participants originally randomized to 30 mg upadacitinib were re-randomized at Week 16 to receive placebo tablets once a day for 72 weeks in Period 2.

Reporting group title

Upadacitinib 30 mg / Upadacitinib 30 mg

Reporting group description

Participants originally randomized to 30 mg upadacitinib were re-randomized at Week 16 to receive 30 mg upadacitinib once a day for 72 weeks in Period 2.

Primary: Percent Change from Baseline in Eczema Area and Severity Index (EASI) Score at Week 16

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End point title

Percent Change from Baseline in Eczema Area and Severity Index (EASI) Score at Week 16

End point description

EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none (0), mild (1), moderate (2), or severe (3)) for Redness (erythema, inflammation), Thickness (induration, papulation, swelling – acute eczema), Scratching (excoriation), and Lichenification (lined skin, prurigo nodules – chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease; a negative change from baseline indicates improvement. Last observation carried forward (LOCF) imputation was used.

End point type

Primary

End point timeframe

Baseline and Week 16

End point values	Placebo	Upadacitinib 7.5 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	39 ^[1]	42	42	42
Units: percent change
least squares mean (standard error)	-23.0 ± 6.42	-39.4 ± 6.24	-61.7 ± 6.12	-74.4 ± 6.13

Notes
[1] - Randomized participants with at least one post-baseline assessment

Analysis of % Change From Baseline in EASI

Comparison groups

Upadacitinib 30 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[2]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-51.4

Confidence interval

level

95%

sides

2-sided

lower limit

-66.5

upper limit

-36.3

Variability estimate

Standard error of the mean

Dispersion value

7.65

Notes
[2] - Analysis of covariance (ANCOVA) with stratum (geographic region), baseline value, and treatment in the model.

Analysis of % Change From Baseline in EASI

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[3]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-38.7

Confidence interval

level

95%

sides

2-sided

lower limit

-53.7

upper limit

-23.6

Variability estimate

Standard error of the mean

Dispersion value

7.61

Notes
[3] - Analysis of covariance (ANCOVA) with stratum (geographic region), baseline value, and treatment in the model.

Analysis of % Change From Baseline in EASI

Comparison groups

Placebo v Upadacitinib 7.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.032 ^[4]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-16.4

Confidence interval

level

95%

sides

2-sided

lower limit

-31.4

upper limit

-1.4

Variability estimate

Standard error of the mean

Dispersion value

7.61

Notes
[4] - Analysis of covariance (ANCOVA) with stratum (geographic region), baseline value, and treatment in the model.

Secondary: Percentage of Participants who Achieved a 75% Reduction in EASI Score (EASI 75) at Week 16

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End point title

Percentage of Participants who Achieved a 75% Reduction in EASI Score (EASI 75) at Week 16

End point description

EASI is a tool to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected, and the severity of eczema (scored as none [0], mild [1], moderate [2], or severe [3]) for redness, thickness, scratching, and lichenification are assessed. The EASI score is the sum of the scores for each region and ranges from 0 to 72, where higher scores represent worse disease. An EASI 75 response is defined as at least a 75% reduction (improvement) in EASI score relative to the Baseline value. Participants with missing values at Week 16 were counted as non-responders in this analysis (non-responder imputation).

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Placebo	Upadacitinib 7.5 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	41	42	42	42
Units: percentage of participants
number (not applicable)	9.8	28.6	52.4	69.0

Analysis of EASI 75 at Week 16

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[5]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

58.7

Confidence interval

level

95%

sides

2-sided

lower limit

42.5

upper limit

74.8

Notes
[5] - Cochran-Mantel-Haenszel test, adjusted for stratum (geographic region).

Analysis of EASI 75 at Week 16

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[6]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

42.5

Confidence interval

level

95%

sides

2-sided

lower limit

25.5

upper limit

59.6

Notes
[6] - Cochran-Mantel-Haenszel test, adjusted for stratum (geographic region).

Analysis of EASI 75 at Week 16

Comparison groups

Placebo v Upadacitinib 7.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.022 ^[7]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

18.7

Confidence interval

level

95%

sides

2-sided

lower limit

2.7

upper limit

34.7

Notes
[7] - Cochran-Mantel-Haenszel test, adjusted for stratum (geographic region).

Secondary: Percentage of Participants Achieving an Investigator Global Assessment (IGA) of "0" or "1" at Week 16

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End point title

Percentage of Participants Achieving an Investigator Global Assessment (IGA) of "0" or "1" at Week 16

End point description

Investigator's Global Assessment for Atopic Dermatitis (IGA) was scored on the following scale: 0: Clear (No inflammatory signs of atopic dermatitis) 1: Almost Clear (Just perceptible erythema and just perceptible papulation/infiltration) 2: Mild (Mild erythema and mild papulation/infiltration) 3: Moderate (Moderate erythema and moderate papulation/infiltration) 4: Severe (Severe erythema and severe papulation/infiltration with or without oozing/crusting) The percentage of participants with a score of 0 or 1 at Week 16 is reported. Non-responder imputation was used.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo	Upadacitinib 7.5 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	41	42	42	42
Units: percentage of participants
number (not applicable)	2.4	14.3	31.0	50.0

Analysis of IGA Response at Week 16

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[8]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

46.9

Confidence interval

level

95%

sides

2-sided

lower limit

31.1

upper limit

62.7

Notes
[8] - Cochran-Mantel-Haenszel test, adjusted for stratum (geographic region).

Analysis of IGA Response at Week 16

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[9]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

28.6

Confidence interval

level

95%

sides

2-sided

lower limit

13.8

upper limit

43.4

Notes
[9] - Cochran-Mantel-Haenszel test, adjusted for stratum (geographic region).

Analysis of IGA Response at Week 16

Comparison groups

Placebo v Upadacitinib 7.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.044 ^[10]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

11.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

23.5

Notes
[10] - Cochran-Mantel-Haenszel test, adjusted for stratum (geographic region).

Secondary: Percent Change from Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS)

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End point title

Percent Change from Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS)

End point description

Participants were asked to rate itch in the past 24 hours on a daily basis using a scale from 0 to 10, with 0 being no itch and 10 being the worst imaginable itch. The percent change from Baseline at each week was calculated from a rolling weekly average. Last observation carried forward (LOCF) imputation was used.

End point type

Secondary

End point timeframe

Baseline and Weeks 2, 8, and 16

End point values	Placebo	Upadacitinib 7.5 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	37 ^[11]	40	37	42
Units: units on a scale
least squares mean (standard error)
Week 2 (n = 37, 39, 37, 42)	1.7 ± 5.59	-29.3 ± 5.45	-46.0 ± 5.44	-57.6 ± 5.24
Week 8 (n = 37, 40, 37, 42)	-6.7 ± 7.51	-35.5 ± 7.28	-45.1 ± 7.32	-73.1 ± 7.05
Week 16 (n = 37, 40, 37, 42)	-9.7 ± 8.30	-39.6 ± 8.04	-48.0 ± 8.08	-68.9 ± 7.79

Notes
[11] - Participants with at least one post-baseline measurement

Analysis of % Change in Pruritus NRS at Week 2

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[12]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-59.3

Confidence interval

level

95%

sides

2-sided

lower limit

-72.3

upper limit

-46.3

Variability estimate

Standard error of the mean

Dispersion value

6.58

Notes
[12] - ANCOVA with stratum (geographic region), baseline value, and treatment in the model.

Analysis of % Change in Pruritus NRS at Week 2

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[13]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-47.7

Confidence interval

level

95%

sides

2-sided

lower limit

-61.1

upper limit

-34.3

Variability estimate

Standard error of the mean

Dispersion value

6.78

Notes
[13] - ANCOVA with stratum (geographic region), baseline value, and treatment in the model.

Analysis of % Change in Pruritus NRS at Week 2

Statistical analysis description

The number of subjects included in the analysis of the comparison of Placebo vs Upadacitinib 7.5 mg at Week 2 is 76 subjects, rather than 77 subjects, since 1 subject in the Upadacitinib 7.5 mg had missing data at Week 2.

Comparison groups

Placebo v Upadacitinib 7.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[14]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-31.1

Confidence interval

level

95%

sides

2-sided

lower limit

-44.3

upper limit

-17.8

Variability estimate

Standard error of the mean

Dispersion value

6.7

Notes
[14] - ANCOVA with stratum (geographic region), baseline value, and treatment in the model.

Analysis of % Change in Pruritus NRS at Week 8

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[15]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-66.4

Confidence interval

level

95%

sides

2-sided

lower limit

-83.9

upper limit

-48.9

Variability estimate

Standard error of the mean

Dispersion value

8.85

Notes
[15] - ANCOVA with stratum (geographic region), baseline value, and treatment in the model.

Analysis of % Change in Pruritus NRS at Week 8

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[16]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-38.4

Confidence interval

level

95%

sides

2-sided

lower limit

-56.4

upper limit

-20.4

Variability estimate

Standard error of the mean

Dispersion value

9.13

Notes
[16] - ANCOVA with stratum (geographic region), baseline value, and treatment in the model.

Analysis of % Change in Pruritus NRS at Week 8

Comparison groups

Placebo v Upadacitinib 7.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[17]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-28.9

Confidence interval

level

95%

sides

2-sided

lower limit

-46.6

upper limit

-11.2

Variability estimate

Standard error of the mean

Dispersion value

8.96

Notes
[17] - ANCOVA with stratum (geographic region), baseline value, and treatment in the model.

Analysis of % Change in Pruritus NRS at Week 16

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[18]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-59.2

Confidence interval

level

95%

sides

2-sided

lower limit

-78.6

upper limit

-39.9

Variability estimate

Standard error of the mean

Dispersion value

9.78

Notes
[18] - ANCOVA with stratum (geographic region), baseline value, and treatment in the model.

Analysis of % Change in Pruritus NRS at Week 16

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[19]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-38.3

Confidence interval

level

95%

sides

2-sided

lower limit

-58.3

upper limit

-18.4

Variability estimate

Standard error of the mean

Dispersion value

10.08

Notes
[19] - ANCOVA with stratum (geographic region), baseline value, and treatment in the model.

Analysis of % Change in Pruritus NRS at Week 16

Comparison groups

Placebo v Upadacitinib 7.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[20]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-29.9

Confidence interval

level

95%

sides

2-sided

lower limit

-49.4

upper limit

-10.3

Variability estimate

Standard error of the mean

Dispersion value

9.9

Notes
[20] - ANCOVA with stratum (geographic region), baseline value, and treatment in the model.

Secondary: Percent Change from Baseline in EASI Score at Week 8

Top of page

End point title

Percent Change from Baseline in EASI Score at Week 8

End point description

End point type

Secondary

End point timeframe

Baseline and Week 8

End point values	Placebo	Upadacitinib 7.5 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	39 ^[21]	42	42	42
Units: percent change
least squares mean (standard error)	-17.5 ± 6.27	-43.7 ± 6.09	-65.4 ± 5.97	-82.8 ± 5.98

Notes
[21] - Participants with at least one post-baseline measurement

Analysis of % Change in EASI at Week 8

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[22]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-65.3

Confidence interval

level

95%

sides

2-sided

lower limit

-80

upper limit

-50.5

Variability estimate

Standard error of the mean

Dispersion value

7.46

Notes
[22] - ANCOVA with stratum (geographic region), baseline value, and treatment in the model.

Analysis of % Change in EASI at Week 8

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[23]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-47.9

Confidence interval

level

95%

sides

2-sided

lower limit

-62.6

upper limit

-33.3

Variability estimate

Standard error of the mean

Dispersion value

7.42

Notes
[23] - ANCOVA with stratum (geographic region), baseline value, and treatment in the model.

Analysis of % Change in EASI at Week 8

Comparison groups

Placebo v Upadacitinib 7.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[24]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-26.2

Confidence interval

level

95%

sides

2-sided

lower limit

-40.8

upper limit

-11.5

Variability estimate

Standard error of the mean

Dispersion value

7.42

Notes
[24] - ANCOVA with stratum (geographic region), baseline value, and treatment in the model.

Secondary: Percent Change from Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Weeks 8 and 16

Top of page

End point title

Percent Change from Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Weeks 8 and 16

End point description

SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as a percentage of the whole body (0-100%). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 to 18. Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 to 103 (worst). A negative change from Baseline indicates improvement. Last observation carried forward imputation was used.

End point type

Secondary

End point timeframe

Baseline and Weeks 8 and 16

End point values	Placebo	Upadacitinib 7.5 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	33 ^[25]	39	36	40
Units: percent change
least squares mean (standard error)
Week 8	-7.0 ± 5.84	-35.4 ± 5.53	-44.1 ± 5.69	-65.3 ± 5.52
Week 16	-12.4 ± 5.97	-32.5 ± 5.66	-46.9 ± 5.82	-60.4 ± 5.65

Notes
[25] - Participants with Baseline and at least one post-baseline measurement

Analysis of % Change in SCORAD at Week 8

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[26]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-58.3

Confidence interval

level

95%

sides

2-sided

lower limit

-71.7

upper limit

-44.9

Variability estimate

Standard error of the mean

Dispersion value

6.78

Notes
[26] - ANCOVA with stratum (geographic region), baseline value, and treatment in the model.

Analysis of % Change in SCORAD at Week 8

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[27]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-37.1

Confidence interval

level

95%

sides

2-sided

lower limit

-50.8

upper limit

-23.4

Variability estimate

Standard error of the mean

Dispersion value

6.94

Notes
[27] - ANCOVA with stratum (geographic region), baseline value, and treatment in the model.

Analysis of % Change in SCORAD at Week 8

Comparison groups

Placebo v Upadacitinib 7.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[28]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-28.4

Confidence interval

level

95%

sides

2-sided

lower limit

-41.9

upper limit

-15

Variability estimate

Standard error of the mean

Dispersion value

6.81

Notes
[28] - ANCOVA with stratum (geographic region), baseline value, and treatment in the model.

Analysis of % Change in SCORAD at Week 16

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[29]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-48

Confidence interval

level

95%

sides

2-sided

lower limit

-61.7

upper limit

-34.3

Variability estimate

Standard error of the mean

Dispersion value

6.93

Notes
[29] - ANCOVA with stratum (geographic region), baseline value, and treatment in the model.

Analysis of % Change in SCORAD at Week 16

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[30]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-34.5

Confidence interval

level

95%

sides

2-sided

lower limit

-48.5

upper limit

-20.5

Variability estimate

Standard error of the mean

Dispersion value

7.1

Notes
[30] - ANCOVA with stratum (geographic region), baseline value, and treatment in the model.

Analysis of % Change in SCORAD at Week 16

Comparison groups

Placebo v Upadacitinib 7.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004 ^[31]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-20.2

Confidence interval

level

95%

sides

2-sided

lower limit

-33.9

upper limit

-6.4

Variability estimate

Standard error of the mean

Dispersion value

6.96

Notes
[31] - ANCOVA with stratum (geographic region), baseline value, and treatment in the model.

Secondary: Percentage of Participants who Achieved an EASI 75 Response at Week 8

Top of page

End point title

Percentage of Participants who Achieved an EASI 75 Response at Week 8

End point description

EASI is a tool to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected, and the severity of eczema (scored as none [0], mild [1], moderate [2], or severe [3]) for redness, thickness, scratching, and lichenification are assessed. The EASI score is the sum of the scores for each region and ranges from 0 to 72, where higher scores represent worse disease. An EASI 75 response is defined as at least a 75% reduction (improvement) in EASI score relative to the Baseline value. Participants with missing values at Week 8 were counted as non-responders in this analysis (non-responder imputation).

End point type

Secondary

End point timeframe

Baseline and Week 8

End point values	Placebo	Upadacitinib 7.5 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	41	42	42	42
Units: percentage of participants
number (not applicable)	7.3	31.0	52.4	81.0

Analysis of EASI 75 Response at Week 8

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[32]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

72.7

Confidence interval

level

95%

sides

2-sided

lower limit

58.3

upper limit

87.1

Notes
[32] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of EASI 75 Response at Week 8

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[33]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

44.9

Confidence interval

level

95%

sides

2-sided

lower limit

27.9

upper limit

61.9

Notes
[33] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of EASI 75 Response at Week 8

Comparison groups

Placebo v Upadacitinib 7.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004 ^[34]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

23.4

Confidence interval

level

95%

sides

2-sided

lower limit

7.5

upper limit

39.4

Notes
[34] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Secondary: Percentage of Participants who Achieved an EASI 50 Response at Weeks 8 and 16

Top of page

End point title

Percentage of Participants who Achieved an EASI 50 Response at Weeks 8 and 16

End point description

EASI is a tool to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected, and the severity of eczema (scored as none [0], mild [1], moderate [2], or severe [3]) for redness, thickness, scratching, and lichenification are assessed. The EASI score is the sum of the scores for each region and ranges from 0 to 72, where higher scores represent worse disease. An EASI 50 response is defined as at least a 50% reduction (improvement) in EASI score relative to the Baseline value. Participants with missing values at each time point were counted as non-responders in this analysis (non-responder imputation).

End point type

Secondary

End point timeframe

Baseline and Weeks 8 and 16

End point values	Placebo	Upadacitinib 7.5 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	41	42	42	42
Units: percentage of participants
number (not applicable)
Week 8	22.0	54.8	71.4	92.9
Week 16	22.0	50.0	71.4	83.3

Analysis of EASI 50 Response at Week 8

Comparison groups

Upadacitinib 30 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[35]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

70.7

Confidence interval

level

95%

sides

2-sided

lower limit

56.2

upper limit

85.2

Notes
[35] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of EASI 50 Response at Week 8

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[36]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

30.8

upper limit

67.3

Notes
[36] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of EASI 50 Response at Week 8

Comparison groups

Placebo v Upadacitinib 7.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[37]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

32.8

Confidence interval

level

95%

sides

2-sided

lower limit

13.4

upper limit

52.2

Notes
[37] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of EASI 50 Response at Week 16

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[38]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

60.6

Confidence interval

level

95%

sides

2-sided

lower limit

45.3

upper limit

75.9

Notes
[38] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of EASI 50 Response at Week 16

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[39]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

48.6

Confidence interval

level

95%

sides

2-sided

lower limit

31.3

upper limit

65.9

Notes
[39] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of EASI 50 Response at Week 16

Comparison groups

Placebo v Upadacitinib 7.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[40]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

28.2

Confidence interval

level

95%

sides

2-sided

lower limit

9.8

upper limit

46.6

Notes
[40] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Secondary: Percentage of Participants who Achieved an EASI 90 Response at Weeks 8 and 16

Top of page

End point title

Percentage of Participants who Achieved an EASI 90 Response at Weeks 8 and 16

End point description

EASI is a tool to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected, and the severity of eczema (scored as none [0], mild [1], moderate [2], or severe [3]) for redness, thickness, scratching, and lichenification are assessed. The EASI score is the sum of the scores for each region and ranges from 0 to 72, where higher scores represent worse disease. An EASI 90 response is defined as at least a 90% reduction (improvement) in EASI score relative to the Baseline value. Participants with missing values at Week 16 were counted as non-responders in this analysis (non-responder imputation).

End point type

Secondary

End point timeframe

Baseline and Weeks 8 and 16

End point values	Placebo	Upadacitinib 7.5 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	41	42	42	42
Units: percentage of participants
number (not applicable)
Week 8	0.0	9.5	26.2	45.2
Week 16	2.4	14.3	26.2	50.0

Analysis of EASI 90 Response at Week 8

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[41]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

43.8

Confidence interval

level

95%

sides

2-sided

lower limit

29.1

upper limit

58.5

Notes
[41] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of EASI 90 Response at Week 8

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[42]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

26.1

Confidence interval

level

95%

sides

2-sided

lower limit

12.6

upper limit

39.6

Notes
[42] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of EASI 90 Response at Week 8

Comparison groups

Placebo v Upadacitinib 7.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.051 ^[43]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

9.4

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

18.8

Notes
[43] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of EASI 90 Response at Week 16

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[44]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

46.9

Confidence interval

level

95%

sides

2-sided

lower limit

31.3

upper limit

62.4

Notes
[44] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of EASI 90 Response at Week 16

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[45]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

23.8

Confidence interval

level

95%

sides

2-sided

lower limit

9.6

upper limit

38.1

Notes
[45] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of EASI 90 Response at Week 16

Comparison groups

Placebo v Upadacitinib 7.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.049 ^[46]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

11.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

23.6

Notes
[46] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Secondary: Percentage of Participants who Achieved a SCORAD 50 Response at Weeks 8 and 16

Top of page

End point title

Percentage of Participants who Achieved a SCORAD 50 Response at Weeks 8 and 16

End point description

A SCORAD 50 response is defined as at least a 50% reduction (improvement) in SCORAD score relative to the Baseline value. SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as a percentage of the whole body (0-100%). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 to 18. Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 to 103 (worst). Non-responder imputation was used.

End point type

Secondary

End point timeframe

Baseline and Weeks 8 and 16

End point values	Placebo	Upadacitinib 7.5 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	41	42	42	42
Units: percentage of participants
number (not applicable)
Week 8	7.3	33.3	42.9	76.2
Week 16	7.3	28.6	42.9	61.9

Analysis of SCORAD 50 Response at Week 8

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[47]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

68.4

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

82.8

Notes
[47] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of SCORAD 50 Response at Week 8

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[48]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

35.3

Confidence interval

level

95%

sides

2-sided

lower limit

18.5

upper limit

52.2

Notes
[48] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of SCORAD 50 Response at Week 8

Comparison groups

Placebo v Upadacitinib 7.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[49]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

25.7

Confidence interval

level

95%

sides

2-sided

lower limit

9.6

upper limit

41.7

Notes
[49] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of SCORAD 50 Response at Week 16

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[50]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

54.5

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

69.9

Notes
[50] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of SCORAD 50 Response at Week 16

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[51]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

35.8

Confidence interval

level

95%

sides

2-sided

lower limit

19.1

upper limit

52.5

Notes
[51] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of SCORAD 50 Response at Week 16

Comparison groups

Placebo v Upadacitinib 7.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.008 ^[52]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

21.2

Confidence interval

level

95%

sides

2-sided

lower limit

5.7

upper limit

36.8

Notes
[52] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Secondary: Percentage of Participants who Achieved a SCORAD 75 Response at Weeks 8 and 16

Top of page

End point title

Percentage of Participants who Achieved a SCORAD 75 Response at Weeks 8 and 16

End point description

A SCORAD 75 response is defined as at least a 75% reduction (improvement) in SCORAD score relative to the Baseline value. SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as a percentage of the whole body (0-100%). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 to 18. Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 to 103 (worst). Non-responder imputation was used.

End point type

Secondary

End point timeframe

Baseline and Weeks 8 and 16

End point values	Placebo	Upadacitinib 7.5 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	41	42	42	42
Units: percentage of participants
number (not applicable)
Week 8	0.0	9.5	9.5	31.0
Week 16	2.4	4.8	21.4	40.5

Analysis of SCORAD 75 Response at Week 8

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[53]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

30.4

Confidence interval

level

95%

sides

2-sided

lower limit

16.2

upper limit

44.6

Notes
[53] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of SCORAD 75 Response at Week 8

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.052 ^[54]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

9.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

18.9

Notes
[54] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of SCORAD 75 Response at Week 8

Comparison groups

Placebo v Upadacitinib 7.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.048 ^[55]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

9.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

18.5

Notes
[55] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of SCORAD 75 Response at Week 16

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[56]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

37.7

Confidence interval

level

95%

sides

2-sided

lower limit

22.2

upper limit

53.3

Notes
[56] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of SCORAD 75 Response at Week 16

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006 ^[57]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

5.6

upper limit

32.5

Notes
[57] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of SCORAD 75 Response at Week 16

Comparison groups

Upadacitinib 7.5 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.581 ^[58]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-6

upper limit

10.8

Notes
[58] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Secondary: Percentage of Participants who Achieved a SCORAD 90 Response at Weeks 8 and 16

Top of page

End point title

Percentage of Participants who Achieved a SCORAD 90 Response at Weeks 8 and 16

End point description

A SCORAD 90 response is defined as at least a 90% reduction (improvement) in SCORAD score relative to the Baseline value. SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as a percentage of the whole body (0-100%). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 to 18. Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 to 103 (worst). Non-responder imputation was used.

End point type

Secondary

End point timeframe

Baseline and Weeks 8 and 16

End point values	Placebo	Upadacitinib 7.5 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	41	42	42	42
Units: percentage of participants
number (not applicable)
Week 8	0.0	4.8	2.4	14.3
Week 16	0.0	2.4	9.5	23.8

Analysis of SCORAD 90 Response at Week 8

Comparison groups

Upadacitinib 30 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012 ^[59]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

14.2

Confidence interval

level

95%

sides

2-sided

lower limit

3.2

upper limit

25.2

Notes
[59] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of SCORAD 90 Response at Week 8

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.428 ^[60]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

2.3

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

Notes
[60] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of SCORAD 90 Response at Week 8

Comparison groups

Placebo v Upadacitinib 7.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.206 ^[61]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

4.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

11.8

Notes
[61] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of SCORAD 90 Response at Week 16

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[62]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

23.3

Confidence interval

level

95%

sides

2-sided

lower limit

10.4

upper limit

36.2

Notes
[62] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of SCORAD 90 Response at Week 16

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.048 ^[63]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

9.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

18.8

Notes
[63] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of SCORAD 90 Response at Week 16

Comparison groups

Placebo v Upadacitinib 7.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.426 ^[64]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

8.1

Notes
[64] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Secondary: Change from Baseline in Percentage of Body Surface Area (BSA) Affected by Atopic Dermatitis at Week 16

Top of page

End point title

Change from Baseline in Percentage of Body Surface Area (BSA) Affected by Atopic Dermatitis at Week 16

End point description

Body surface area (BSA) affected by atopic dermatitis was assessed by the physician and is expressed as a percentage of the total BSA. For purposes of the estimation, the total surface of the participant's palm plus five digits was assumed to be approximately equivalent to 1% BSA. Last observation carried forward imputation was used.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Placebo	Upadacitinib 7.5 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	39 ^[65]	42	42	42
Units: percentage of body surface area
least squares mean (standard error)	-4.1 ± 3.58	-11.7 ± 3.48	-27.1 ± 3.43	-30.7 ± 3.43

Notes
[65] - Participants with at least one post-baseline measurement

Analysis of Change in BSA at Week 16

Comparison groups

Upadacitinib 30 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[66]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-26.5

Confidence interval

level

95%

sides

2-sided

lower limit

-34.9

upper limit

-18.1

Variability estimate

Standard error of the mean

Dispersion value

4.25

Notes
[66] - ANCOVA with stratum (geographic region), baseline value, and treatment in the model.

Analysis of Change in BSA at Week 16

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[67]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-23

Confidence interval

level

95%

sides

2-sided

lower limit

-31.4

upper limit

-14.6

Variability estimate

Standard error of the mean

Dispersion value

4.27

Notes
[67] - ANCOVA with stratum (geographic region), baseline value, and treatment in the model.

Analysis of Change in BSA at Week 16

Comparison groups

Placebo v Upadacitinib 7.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.075 ^[68]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-7.6

Confidence interval

level

95%

sides

2-sided

lower limit

-16

upper limit

0.8

Variability estimate

Standard error of the mean

Dispersion value

4.25

Notes
[68] - ANCOVA with stratum (geographic region), baseline value, and treatment in the model.

Secondary: Percentage of Participants with Reduction of ≥ 4 Points from Baseline in Pruritus NRS at Week 16

Top of page

End point title

Percentage of Participants with Reduction of ≥ 4 Points from Baseline in Pruritus NRS at Week 16

End point description

Participants were asked to rate itch in the past 24 hours on a daily basis using a scale from 0 to 10, with 0 being no itch and 10 being the worst imaginable itch. The percentage of participants with reduction of ≥ 4 points from Baseline in pruritus NRS was assessed in participants with a baseline pruritus NRS of ≥ 4. Non-responder imputation was used.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Placebo	Upadacitinib 7.5 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	35 ^[69]	37	32	36
Units: percentage of participants
number (not applicable)	5.7	24.3	59.4	52.8

Notes
[69] - Participants with Baseline pruritus NRS of ≥ 4

Analysis of Reduction in Pruritus NRS ≥ 4 Points

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[70]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

47.4

Confidence interval

level

95%

sides

2-sided

lower limit

29.6

upper limit

65.2

Notes
[70] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of Reduction in Pruritus NRS ≥ 4 Points

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[71]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

53.4

Confidence interval

level

95%

sides

2-sided

lower limit

35.5

upper limit

71.3

Notes
[71] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Analysis of Reduction in Pruritus NRS ≥ 4 Points

Comparison groups

Placebo v Upadacitinib 7.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.021 ^[72]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

18.6

Confidence interval

level

95%

sides

2-sided

lower limit

2.8

upper limit

34.3

Notes
[72] - Cochran-Mantel-Haenszel test adjusted for stratum (geographic region).

Secondary: Percent Change from Re-randomization (Week 16) in EASI Score in Period 2

Top of page

End point title

Percent Change from Re-randomization (Week 16) in EASI Score in Period 2

End point description

End point type

Secondary

End point timeframe

Re-randomization (Week 16) and Weeks 20, 24, 32, 40, 52, 64, 76, and 88

End point values	Placebo / Placebo	Placebo / Upadacitinib 30 mg	Upadacitinib 7.5 mg / Placebo	Upadacitinib 7.5 mg / Upadacitinib 7.5 mg	Upadacitinib 15 mg / Placebo	Upadacitinib 15 mg / Upadacitinib 15 mg	Upadacitinib 30 mg / Placebo	Upadacitinib 30 mg / Upadacitinib 30 mg
Number of subjects analysed	10	10	15	15	17	18 ^[73]	14 ^[74]	19 ^[75]
Units: percent change
least squares mean (standard error)
Week 20	50.7 ± 33.50	11.8 ± 30.59	186.0 ± 46.53	79.1 ± 48.42	582.3 ± 172.19	65.7 ± 178.24	791.5 ± 262.34	-73.8 ± 215.54
Week 24	13.5 ± 17.13	-67.5 ± 15.64	189.6 ± 44.17	59.0 ± 45.97	607.3 ± 169.49	72.6 ± 175.44	898.5 ± 248.78	-69.6 ± 200.01
Week 32	-2.3 ± 15.15	-83.1 ± 13.83	181.5 ± 44.74	63.5 ± 46.56	613.3 ± 169.63	151.7 ± 175.59	771.5 ± 252.90	-28.8 ± 210.78
Week 40	-31.2 ± 18.16	-92.0 ± 16.58	200.9 ± 41.58	77.6 ± 43.27	608.8 ± 169.95	154.1 ± 175.92	778.9 ± 344.45	140.6 ± 293.17
Week 52	-29.8 ± 17.74	-90.1 ± 16.20	189.1 ± 43.65	74.4 ± 45.42	613.8 ± 166.85	104.1 ± 164.05	799.5 ± 254.30	-13.3 ± 216.44
Week 64	-35.8 ± 17.34	-91.4 ± 15.83	179.9 ± 44.91	71.8 ± 46.74	614.6 ± 166.57	104.1 ± 163.78	802.1 ± 278.76	63.6 ± 237.26
Week 76	-37.3 ± 19.09	-90.3 ± 17.43	201.4 ± 41.89	77.7 ± 43.60	614.0 ± 168.03	130.2 ± 169.29	787.8 ± 262.89	24.4 ± 219.11
Week 88	-37.7 ± 19.18	-84.6 ± 17.51	170.7 ± 46.87	69.1 ± 48.78	617.5 ± 165.84	99.3 ± 163.06	769.7 ± 265.64	39.0 ± 226.10

Notes
[73] - n = 16 at Weeks 20, 24, 32, and 40; n = 17 at Week 76
[74] - n = 13 at Weeks 20, 24
[75] - n = 18 at Weeks 20, 40, 52, 64, and 88

No statistical analyses for this end point

Secondary: Percentage of Participants with an EASI 75 Response in Period 2 in Participants who were Re-randomized as EASI 75 Non-responders at Week 16

Top of page

End point title

Percentage of Participants with an EASI 75 Response in Period 2 in Participants who were Re-randomized as EASI 75 Non-responders at Week 16

End point description

EASI is a tool to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected, and the severity of eczema (scored as none [0], mild [1], moderate [2], or severe [3]) for redness, thickness, scratching, and lichenification are assessed. The EASI score is the sum of the scores for each region and ranges from 0 to 72, where higher scores represent worse disease. An EASI 75 response is defined as at least a 75% reduction (improvement) in EASI score relative to the Baseline value, and was analyzed in participants who were re-randomized at Week 16 and were EASI 75 non-responders at Week 16.

End point type

Secondary

End point timeframe

Weeks 20, 24, 32, 40, 52, 64, 76, and 88

End point values	Placebo / Placebo	Placebo / Upadacitinib 30 mg	Upadacitinib 7.5 mg / Placebo	Upadacitinib 7.5 mg / Upadacitinib 7.5 mg	Upadacitinib 15 mg / Placebo	Upadacitinib 15 mg / Upadacitinib 15 mg	Upadacitinib 30 mg / Placebo	Upadacitinib 30 mg / Upadacitinib 30 mg
Number of subjects analysed	9	8	10	11	7	8	5	4
Units: percentage of participants
number (not applicable)
Week 20 (n = 9, 8, 10, 11, 7, 8, 5, 4)	11.1	12.5	0	9.1	0	12.5	20.0	25.0
Week 24 (n = 1, 7, 0, 3, 1, 2, 3, 3)	100	85.7	0	33.3	0	0	33.3	33.3
Week 32 (n = 1, 6, 0, 2, 1, 2, 2, 2)	100	100	0	0	0	50.0	50.0	50.0
Week 40 (n = 1, 6, 0, 0, 1, 1, 1, 2)	100	66.7	0	0	0	100	0	50.0
Week 52 (n = 1, 6, 0, 0, 1, 1, 0, 2)	100	66.7	0	0	0	100	0	50.0
Week 64 (n = 1, 5, 0, 0, 1, 1, 0, 1)	100	80.0	0	0	0	100	0	100
Week 76 (n = 1, 3, 0, 0, 1, 1, 0, 1)	100	100	0	0	0	100	0	100
Week 88 (n = 1, 2, 0, 0, 1, 1, 0, 1)	100	100	0	0	0	100	0	100

No statistical analyses for this end point

Secondary: Percentage of Participants who Achieved a Dermatology Life Quality Index (DLQI) = "0" or "1" at Weeks 8 and 16

Top of page

End point title

Percentage of Participants who Achieved a Dermatology Life Quality Index (DLQI) = "0" or "1" at Weeks 8 and 16

End point description

The DLQI is a 10-item questionnaire that asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week in the following 6 aspects: symptoms and feelings, daily activities, leisure, work or school activities, personal relationships and treatment related feelings. Participants answer the 10 questions on a scale from 0 (not at all) to 3 (very much). The DLQI is calculated by summing the scores of the 10 questions, resulting in a maximum of 30 and a minimum of 0 with higher scores indicating more impaired quality of life. A score of 0 or 1 means that the disease has no effect at all. Dermatology Life Quality Index outcomes were defined but are not reported because of an error in the programming of the electronic device used to administer the questionnaire that precluded determination of these outcomes.

End point type

Secondary

End point timeframe

Baseline and Weeks 8 and 16

End point values	Placebo	Upadacitinib 7.5 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	0 ^[76]	0 ^[77]	0 ^[78]	0 ^[79]
Units: percentage of participants
number (not applicable)

Notes
[76] - Not reported due to an error in the electronic device used to administer the questionnaire
[77] - Not reported due to an error in the electronic device used to administer the questionnaire
[78] - Not reported due to an error in the electronic device used to administer the questionnaire
[79] - Not reported due to an error in the electronic device used to administer the questionnaire

No statistical analyses for this end point

Secondary: Change from Baseline in DLQI at Weeks 8 and 16

Top of page

End point title

Change from Baseline in DLQI at Weeks 8 and 16

End point description

The DLQI is a 10-item questionnaire that asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week in the following 6 aspects: symptoms and feelings, daily activities, leisure, work or school activities, personal relationships and treatment related feelings. Participants answer the 10 questions on a scale from 0 (not at all) to 3 (very much). The DLQI is calculated by summing the scores of the 10 questions, resulting in a maximum of 30 and a minimum of 0 with higher scores indicating more impaired quality of life. A negative change from Baseline indicates improvement. Dermatology Life Quality Index outcomes were defined but are not reported because of an error in the programming of the electronic device used to administer the questionnaire that precluded determination of these outcomes.

End point type

Secondary

End point timeframe

Baseline and Weeks 8 and 16

End point values	Placebo	Upadacitinib 7.5 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	0 ^[80]	0 ^[81]	0 ^[82]	0 ^[83]
Units: scores on a scale
least squares mean (standard error)	±	±	±	±

Notes
[80] - Not reported due to an error in the electronic device used to administer the questionnaire
[81] - Not reported due to an error in the electronic device used to administer the questionnaire
[82] - Not reported due to an error in the electronic device used to administer the questionnaire
[83] - Not reported due to an error in the electronic device used to administer the questionnaire

No statistical analyses for this end point

Secondary: Time to Loss of EASI 50 Response Relative to Baseline Among Participants Re-randomized as EASI 75 Responders at Week 16

Top of page

End point title

Time to Loss of EASI 50 Response Relative to Baseline Among Participants Re-randomized as EASI 75 Responders at Week 16

End point description

Time to loss of EASI 50 response in Period 2 relative to Baseline among those who were re-randomized as EASI 75 responders at Week 16. Time to loss of EASI 50 response was measured from Week 16 to the date of the first assessment in Period 2 where a participant's EASI score was higher than 50% of their Baseline score. Participants with no loss of response were censored at their last treatment visit or the start of rescue treatment, whichever occurred first. "99999" indicates data that could not be estimated due to a low number of events.

End point type

Secondary

End point timeframe

From re-randomization at Week 16 until Week 88

End point values	Placebo / Placebo	Placebo / Upadacitinib 30 mg	Upadacitinib 7.5 mg / Placebo	Upadacitinib 7.5 mg / Upadacitinib 7.5 mg	Upadacitinib 15 mg / Placebo	Upadacitinib 15 mg / Upadacitinib 15 mg	Upadacitinib 30 mg / Placebo	Upadacitinib 30 mg / Upadacitinib 30 mg
Number of subjects analysed	1	2	5	5	12	10	14	15
Units: days
median (confidence interval 95%)	99999 (99999 to 99999)	99999 (99999 to 99999)	29 (27 to 99999)	99999 (29 to 99999)	30 (17 to 55)	114 (29 to 99999)	28 (25 to 36)	99999 (99999 to 99999)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From the first dose of study drug up to 30 days after last dose. Period 1: 16 weeks, Period 2: 72 weeks.

Adverse event reporting additional description

Any AE that occurred on or after the first dose of upadacitinib 30 mg rescue therapy is counted in the Period 1+2: Upadacitinib 30 mg group. Participants who received rescue therapy after placebo, upadacitinib 7.5 or 15 mg treatment in Period 2 are counted in both Period 1+2: Placebo/Upadacitinib 7.5/15 mg and Period 1+2: Upadacitinib 30 mg groups.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.1

Reporting group title

Period 1: Placebo

Reporting group description

Participants received placebo once daily (QD) for 16 weeks in Period 1.

Reporting group title

Period 1: Upadacitinib 15 mg

Reporting group description

Participants received upadacitinib 15 mg once daily for 16 weeks in Period 1.

Reporting group title

Period 1: Upadacitinib 7.5 mg

Reporting group description

Participants received upadacitinib 7.5 mg once daily for 16 weeks in Period 1.

Reporting group title

Period 1: Upadacitinib 30 mg

Reporting group description

Participants received upadacitinib 30 mg once daily for 16 weeks in Period 1.

Reporting group title

Period 1+2: Upadacitinib 7.5 mg

Reporting group description

Participants originally randomized to upadacitinib 7.5 mg received upadacitinib 7.5 mg once daily for 16 weeks in Period 1; Participants re-randomized to upadacitinib 7.5 mg in Period 2 continued to receive upadacitinib 7.5 mg for 72 weeks in Period 2 or until rescue.

Reporting group title

Period 1+2: Upadacitinib 15 mg

Reporting group description

Participants originally randomized to upadacitinib 15 mg received upadacitinib 15 mg once daily for 16 weeks in Period 1; Participants re-randomized to upadacitinib 15 mg in Period 2 continued to receive upadacitinib 15 mg for 72 weeks in Period 2 or until rescue.

Reporting group title

Period 1+2: Upadacitinib 30 mg

Reporting group description

Participants originally randomized to upadacitinib 30 mg received upadacitinib 30 mg once daily for 16 weeks in Period 1. Participants re-randomized to upadacitinib 30 mg in Period 2 continued to receive upadacitinib 30 mg for 72 weeks in Period 2. Participants originally randomized to placebo and re-randomized to upadacitinib 30 mg at Week 16 received upadacitinib 30 mg from Week 16 to Week 88. Participants re-randomized to upadacitinib 7.5 mg or 15 mg at Week 16 who were rescued starting at Week 20 or later received upadacitinib 30 mg until Week 88.

Reporting group title

Period 1+2: Placebo

Reporting group description

Participants originally randomized to placebo received placebo once daily for 16 weeks in Period 1. Participants re-randomized to placebo in Period 2 continued to receive placebo for 72 weeks in Period 2 or until rescue.

Serious adverse events	Period 1: Placebo	Period 1: Upadacitinib 15 mg	Period 1: Upadacitinib 7.5 mg	Period 1: Upadacitinib 30 mg	Period 1+2: Upadacitinib 7.5 mg	Period 1+2: Upadacitinib 15 mg	Period 1+2: Upadacitinib 30 mg	Period 1+2: Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 40 (2.50%)	1 / 42 (2.38%)	2 / 42 (4.76%)	0 / 42 (0.00%)	2 / 42 (4.76%)	1 / 42 (2.38%)	7 / 114 (6.14%)	1 / 93 (1.08%)
number of deaths (all causes)	0	0	0	0	0	0	2	0
number of deaths resulting from adverse events	0	0	0	0	0	0	2	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SQUAMOUS CELL CARCINOMA OF SKIN
subjects affected / exposed	0 / 40 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 114 (0.88%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
ATRIAL FIBRILLATION
subjects affected / exposed	1 / 40 (2.50%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 114 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CARDIO-RESPIRATORY ARREST
subjects affected / exposed	0 / 40 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 114 (0.88%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
PERICARDITIS
subjects affected / exposed	0 / 40 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 114 (0.88%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
Gastrointestinal disorders
OESOPHAGEAL FISTULA
subjects affected / exposed	0 / 40 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 114 (0.88%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
subjects affected / exposed	0 / 40 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 114 (0.88%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	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
subjects affected / exposed	0 / 40 (0.00%)	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 114 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	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
Renal and urinary disorders
URETEROLITHIASIS
subjects affected / exposed	0 / 40 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 114 (0.88%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS
subjects affected / exposed	0 / 40 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 114 (0.88%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ROTATOR CUFF SYNDROME
subjects affected / exposed	0 / 40 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 114 (0.88%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
APPENDICITIS
subjects affected / exposed	0 / 40 (0.00%)	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 114 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	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
PERICORONITIS
subjects affected / exposed	0 / 40 (0.00%)	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 114 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	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
SEPSIS
subjects affected / exposed	0 / 40 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 114 (0.88%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
SKIN INFECTION
subjects affected / exposed	0 / 40 (0.00%)	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 114 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	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	Period 1: Placebo	Period 1: Upadacitinib 15 mg	Period 1: Upadacitinib 7.5 mg	Period 1: Upadacitinib 30 mg	Period 1+2: Upadacitinib 7.5 mg	Period 1+2: Upadacitinib 15 mg	Period 1+2: Upadacitinib 30 mg	Period 1+2: Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	15 / 40 (37.50%)	17 / 42 (40.48%)	21 / 42 (50.00%)	21 / 42 (50.00%)	23 / 42 (54.76%)	22 / 42 (52.38%)	68 / 114 (59.65%)	19 / 93 (20.43%)
Investigations
BLOOD CREATINE PHOSPHOKINASE INCREASED
subjects affected / exposed	2 / 40 (5.00%)	3 / 42 (7.14%)	0 / 42 (0.00%)	4 / 42 (9.52%)	0 / 42 (0.00%)	3 / 42 (7.14%)	7 / 114 (6.14%)	3 / 93 (3.23%)
occurrences all number	2	3	0	4	0	3	8	3
Injury, poisoning and procedural complications
LIGAMENT SPRAIN
subjects affected / exposed	2 / 40 (5.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 114 (0.88%)	2 / 93 (2.15%)
occurrences all number	2	0	0	0	0	0	1	2
Nervous system disorders
HEADACHE
subjects affected / exposed	1 / 40 (2.50%)	3 / 42 (7.14%)	3 / 42 (7.14%)	4 / 42 (9.52%)	3 / 42 (7.14%)	3 / 42 (7.14%)	7 / 114 (6.14%)	2 / 93 (2.15%)
occurrences all number	1	3	3	4	3	3	7	2
Gastrointestinal disorders
DIARRHOEA
subjects affected / exposed	2 / 40 (5.00%)	2 / 42 (4.76%)	2 / 42 (4.76%)	0 / 42 (0.00%)	2 / 42 (4.76%)	2 / 42 (4.76%)	2 / 114 (1.75%)	2 / 93 (2.15%)
occurrences all number	2	4	2	0	2	5	2	2
NAUSEA
subjects affected / exposed	1 / 40 (2.50%)	1 / 42 (2.38%)	3 / 42 (7.14%)	3 / 42 (7.14%)	3 / 42 (7.14%)	1 / 42 (2.38%)	6 / 114 (5.26%)	2 / 93 (2.15%)
occurrences all number	1	1	3	3	3	1	8	2
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN
subjects affected / exposed	0 / 40 (0.00%)	0 / 42 (0.00%)	3 / 42 (7.14%)	0 / 42 (0.00%)	3 / 42 (7.14%)	0 / 42 (0.00%)	0 / 114 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	3	0	3	0	0	0
Skin and subcutaneous tissue disorders
ACNE
subjects affected / exposed	1 / 40 (2.50%)	2 / 42 (4.76%)	4 / 42 (9.52%)	6 / 42 (14.29%)	4 / 42 (9.52%)	2 / 42 (4.76%)	13 / 114 (11.40%)	1 / 93 (1.08%)
occurrences all number	1	2	6	7	6	2	14	1
DERMATITIS ATOPIC
subjects affected / exposed	2 / 40 (5.00%)	2 / 42 (4.76%)	5 / 42 (11.90%)	4 / 42 (9.52%)	6 / 42 (14.29%)	5 / 42 (11.90%)	22 / 114 (19.30%)	2 / 93 (2.15%)
occurrences all number	2	2	6	5	7	5	25	2
DERMATITIS CONTACT
subjects affected / exposed	2 / 40 (5.00%)	1 / 42 (2.38%)	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 42 (0.00%)	1 / 42 (2.38%)	2 / 114 (1.75%)	2 / 93 (2.15%)
occurrences all number	2	1	0	1	0	1	2	2
Renal and urinary disorders
HAEMATURIA
subjects affected / exposed	2 / 40 (5.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 114 (0.88%)	2 / 93 (2.15%)
occurrences all number	2	0	0	0	0	0	1	2
PROTEINURIA
subjects affected / exposed	2 / 40 (5.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 114 (0.88%)	2 / 93 (2.15%)
occurrences all number	2	0	0	0	0	0	1	2
Infections and infestations
HERPES ZOSTER
subjects affected / exposed	0 / 40 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	10 / 114 (8.77%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	10	0
IMPETIGO
subjects affected / exposed	0 / 40 (0.00%)	0 / 42 (0.00%)	1 / 42 (2.38%)	2 / 42 (4.76%)	1 / 42 (2.38%)	0 / 42 (0.00%)	8 / 114 (7.02%)	0 / 93 (0.00%)
occurrences all number	0	0	1	2	1	0	8	0
INFLUENZA
subjects affected / exposed	0 / 40 (0.00%)	0 / 42 (0.00%)	3 / 42 (7.14%)	0 / 42 (0.00%)	3 / 42 (7.14%)	0 / 42 (0.00%)	3 / 114 (2.63%)	0 / 93 (0.00%)
occurrences all number	0	0	3	0	3	0	4	0
NASOPHARYNGITIS
subjects affected / exposed	1 / 40 (2.50%)	4 / 42 (9.52%)	2 / 42 (4.76%)	3 / 42 (7.14%)	3 / 42 (7.14%)	5 / 42 (11.90%)	11 / 114 (9.65%)	1 / 93 (1.08%)
occurrences all number	1	5	2	3	3	6	16	1
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	4 / 40 (10.00%)	5 / 42 (11.90%)	7 / 42 (16.67%)	5 / 42 (11.90%)	7 / 42 (16.67%)	7 / 42 (16.67%)	26 / 114 (22.81%)	5 / 93 (5.38%)
occurrences all number	4	5	7	9	7	7	47	5
URINARY TRACT INFECTION
subjects affected / exposed	0 / 40 (0.00%)	2 / 42 (4.76%)	2 / 42 (4.76%)	1 / 42 (2.38%)	2 / 42 (4.76%)	2 / 42 (4.76%)	6 / 114 (5.26%)	0 / 93 (0.00%)
occurrences all number	0	2	2	1	2	2	8	0

More information

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Were there any global substantial amendments to the protocol? Yes

25 Jul 2016

- Updated contraception timeline requirements for females and clarified consent requirements in Japan. - Updated Exclusion Criteria for topical treatment criteria. - Updated list of prohibited therapies to remove non-atopic dermatitis related treatments. Updated tanning booth and extended sun exposure criteria. Updated live vaccine timeline requirements for Japan. - Updated requirements for allowed topical corticosteroids for rescue therapy.

18 Oct 2016

- Updated details regarding upadacitinib pharmacokinetic data. - Added discontinuation criteria during Period 1 and Period 2. - Added secondary endpoints for Period 2.

16 Dec 2016

- Updated rescue therapy and Premature Discontinuation Visits for subjects who prematurely discontinue from study drug to improve readability and provide clarity. - Updated Inclusion Criteria to clarify diagnosis, pregnancy testing, and contraception requirements. - Updated Exclusion Criteria - Updated text to clarify administration criteria for vaccines for Prior and Concomitant Therapy - Updated Prohibited Therapy to clarify exceptions for administering live vaccines. - Updated contraception requirements. - Added three new PRO questionnaires. - Added a Week 16 primary endpoint analysis.

07 Jun 2017

- Extended the study from 40 weeks to 88 weeks of treatment. Added visits every 12 weeks post Week 40 (Week 52, Week 64, Week 76, and Week 88). Removed optional visits at Week 28 and Week 36 and added optional Visit 4 weeks post topical rescue therapy. - Updated list of examples of biologic therapies for Prohibited Therapy. - Updated language to require a Visit 4 weeks after receiving topical rescue therapy instead of at Week 28 or Week 36. - Updated blood samples collection schedule to reduce patient burden. - Updated list of AEs of special interest to be consistent with the product safety statistical analysis plan. - Removed Week 8 interim analysis language that is no longer planned. Added Week 32 interim analysis language.

30 Aug 2017

- Updated list of AEs of special interest to be consistent with the current AbbVie list of AEs of special interest.

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 Phase 2b Multicenter, Randomized, Placebo-Controlled, Double-Blind Dose-Ranging Study to Evaluate ABT-494 (Upadacitinib) in Adult Subjects with Moderate to Severe Atopic Dermatitis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percent Change from Baseline in Eczema Area and Severity Index (EASI) Score at Week 16

Primary: Percent Change from Baseline in Eczema Area and Severity Index (EASI) Score at Week 16

Secondary: Percentage of Participants who Achieved a 75% Reduction in EASI Score (EASI 75) at Week 16

Secondary: Percentage of Participants who Achieved a 75% Reduction in EASI Score (EASI 75) at Week 16

Secondary: Percentage of Participants Achieving an Investigator Global Assessment (IGA) of "0" or "1" at Week 16

Secondary: Percentage of Participants Achieving an Investigator Global Assessment (IGA) of "0" or "1" at Week 16

Secondary: Percent Change from Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS)

Secondary: Percent Change from Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS)

Secondary: Percent Change from Baseline in EASI Score at Week 8

Secondary: Percent Change from Baseline in EASI Score at Week 8

Secondary: Percent Change from Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Weeks 8 and 16

Secondary: Percent Change from Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Weeks 8 and 16

Secondary: Percentage of Participants who Achieved an EASI 75 Response at Week 8

Secondary: Percentage of Participants who Achieved an EASI 75 Response at Week 8

Secondary: Percentage of Participants who Achieved an EASI 50 Response at Weeks 8 and 16

Secondary: Percentage of Participants who Achieved an EASI 50 Response at Weeks 8 and 16

Secondary: Percentage of Participants who Achieved an EASI 90 Response at Weeks 8 and 16

Secondary: Percentage of Participants who Achieved an EASI 90 Response at Weeks 8 and 16

Secondary: Percentage of Participants who Achieved a SCORAD 50 Response at Weeks 8 and 16

Secondary: Percentage of Participants who Achieved a SCORAD 50 Response at Weeks 8 and 16

Secondary: Percentage of Participants who Achieved a SCORAD 75 Response at Weeks 8 and 16

Secondary: Percentage of Participants who Achieved a SCORAD 75 Response at Weeks 8 and 16

Secondary: Percentage of Participants who Achieved a SCORAD 90 Response at Weeks 8 and 16

Secondary: Percentage of Participants who Achieved a SCORAD 90 Response at Weeks 8 and 16

Secondary: Change from Baseline in Percentage of Body Surface Area (BSA) Affected by Atopic Dermatitis at Week 16

Secondary: Change from Baseline in Percentage of Body Surface Area (BSA) Affected by Atopic Dermatitis at Week 16

Secondary: Percentage of Participants with Reduction of ≥ 4 Points from Baseline in Pruritus NRS at Week 16

Secondary: Percentage of Participants with Reduction of ≥ 4 Points from Baseline in Pruritus NRS at Week 16

Secondary: Percent Change from Re-randomization (Week 16) in EASI Score in Period 2

Secondary: Percent Change from Re-randomization (Week 16) in EASI Score in Period 2

Secondary: Percentage of Participants with an EASI 75 Response in Period 2 in Participants who were Re-randomized as EASI 75 Non-responders at Week 16

Secondary: Percentage of Participants with an EASI 75 Response in Period 2 in Participants who were Re-randomized as EASI 75 Non-responders at Week 16

Secondary: Percentage of Participants who Achieved a Dermatology Life Quality Index (DLQI) = "0" or "1" at Weeks 8 and 16

Secondary: Percentage of Participants who Achieved a Dermatology Life Quality Index (DLQI) = "0" or "1" at Weeks 8 and 16

Secondary: Change from Baseline in DLQI at Weeks 8 and 16

Secondary: Change from Baseline in DLQI at Weeks 8 and 16

Secondary: Time to Loss of EASI 50 Response Relative to Baseline Among Participants Re-randomized as EASI 75 Responders at Week 16

Secondary: Time to Loss of EASI 50 Response Relative to Baseline Among Participants Re-randomized as EASI 75 Responders at Week 16

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2b Multicenter, Randomized, Placebo-Controlled, Double-Blind Dose-Ranging Study to Evaluate ABT-494 (Upadacitinib) in Adult Subjects with Moderate to Severe Atopic Dermatitis