We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Evaluate Upadacitinib in Adolescents and Adults With Moderate to Severe Atopic Dermatitis (Measure Up 2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03607422
Recruitment Status : Active, not recruiting
First Posted : July 31, 2018
Results First Posted : March 28, 2022
Last Update Posted : March 28, 2022
Sponsor:
Information provided by (Responsible Party):
AbbVie

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Atopic Dermatitis
Interventions Drug: Placebo for Upadacitinib
Drug: Upadacitinib
Enrollment 912
Recruitment Details

Participants were enrolled at 154 study sites in 23 countries across Europe, North America, Oceania, and the Asia-Pacific region.

The study included a 16-week double-blind treatment period followed by an ongoing blinded extension period.

The first 836 adults and adolescents enrolled constituted the Main Study; additional adolescents were enrolled in the Adolescent Substudy to ensure enrollment of a total of 180 adolescent participants overall.

Results are reported up to Week 16.
Pre-assignment Details Participants were randomized equally into 1 of 3 treatment groups, stratified by disease severity (validated Investigator Global Assessment Scale for Atopic Dermatitis [vIGA-AD] moderate [3] vs severe [4]), geographic region (US/Puerto Rico/Canada vs Other), and age (adolescent [ages 12 to 17] vs adult [ages 18 to 75]). Randomization for the adolescent substudy was stratified by disease severity (vIGA-AD 3 vs vIGA-AD 4) and geographic region (US/Puerto Rico/Canada vs Other).
Arm/Group Title Adults: Placebo Adults: Upadacitinib 15 mg QD Adults: Upadacitinib 30 mg QD Adolescents: Placebo Adolescents: Upadacitinib 15 mg QD Adolescents: Upadacitinib 30 mg QD
Hide Arm/Group Description Participants ≥ 18 years old received placebo orally once a day (QD) for 16 weeks. Participants ≥ 18 years old received upadacitinib 15 mg orally once a day for 16 weeks. Participants ≥ 18 years old received upadacitinib 30 mg orally once a day for 16 weeks. Adolescent participants (12 - 17 years old) received placebo orally once a day for 16 weeks. Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks.
Period Title: Overall Study
Started [1] 242 243 247 60 58 62
Completed [2] 204 233 235 55 55 59
Not Completed 38 10 12 5 3 3
Reason Not Completed
Adverse Event             7             3             2             0             2             0
Withdrawal by Subject             11             3             6             2             0             0
Lost to Follow-up             0             0             1             0             0             0
Other             12             4             1             2             0             2
Ongoing at Time of Analysis             8             0             2             1             1             1
[1]
Randomized into study
[2]
Completed Week 16
Arm/Group Title Adults: Placebo Adults: Upadacitinib 15 mg QD Adults: Upadacitinib 30 mg QD Adolescents: Placebo Adolescents: Upadacitinib 15 mg QD Adolescents: Upadacitinib 30 mg QD Total
Hide Arm/Group Description Participants ≥ 18 years old received placebo orally once a day for 16 weeks. Participants ≥ 18 years old received upadacitinib 15 mg orally once a day for 16 weeks. Participants ≥ 18 years old received upadacitinib 30 mg orally once a day for 16 weeks. Adolescent participants received placebo orally once a day for 16 weeks. Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. Total of all reporting groups
Overall Number of Baseline Participants 242 243 247 60 58 62 912
Hide Baseline Analysis Population Description
All randomized participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 242 participants 243 participants 247 participants 60 participants 58 participants 62 participants 912 participants
36.0  (14.08) 35.7  (15.15) 36.7  (15.36) 15.5  (1.67) 15.2  (1.79) 15.8  (1.70) 32.1  (15.66)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 242 participants 243 participants 247 participants 60 participants 58 participants 62 participants 912 participants
12 - 14 years
0
   0.0%
0
   0.0%
0
   0.0%
18
  30.0%
23
  39.7%
15
  24.2%
56
   6.1%
15 - 17 years
0
   0.0%
0
   0.0%
0
   0.0%
42
  70.0%
35
  60.3%
47
  75.8%
124
  13.6%
18 - < 40 years
161
  66.5%
165
  67.9%
161
  65.2%
0
   0.0%
0
   0.0%
0
   0.0%
487
  53.4%
40 - < 65 years
70
  28.9%
63
  25.9%
67
  27.1%
0
   0.0%
0
   0.0%
0
   0.0%
200
  21.9%
≥ 65 years
11
   4.5%
15
   6.2%
19
   7.7%
0
   0.0%
0
   0.0%
0
   0.0%
45
   4.9%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 242 participants 243 participants 247 participants 60 participants 58 participants 62 participants 912 participants
Female
104
  43.0%
102
  42.0%
103
  41.7%
35
  58.3%
38
  65.5%
26
  41.9%
408
  44.7%
Male
138
  57.0%
141
  58.0%
144
  58.3%
25
  41.7%
20
  34.5%
36
  58.1%
504
  55.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 242 participants 243 participants 247 participants 60 participants 58 participants 62 participants 912 participants
Hispanic or Latino
25
  10.3%
18
   7.4%
17
   6.9%
10
  16.7%
12
  20.7%
11
  17.7%
93
  10.2%
Not Hispanic or Latino
217
  89.7%
225
  92.6%
230
  93.1%
50
  83.3%
46
  79.3%
51
  82.3%
819
  89.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 242 participants 243 participants 247 participants 60 participants 58 participants 62 participants 912 participants
American Indian or Alaska Native
5
   2.1%
4
   1.6%
1
   0.4%
0
   0.0%
2
   3.4%
1
   1.6%
13
   1.4%
Asian
52
  21.5%
62
  25.5%
55
  22.3%
6
  10.0%
5
   8.6%
12
  19.4%
192
  21.1%
Native Hawaiian or Other Pacific Islander
1
   0.4%
0
   0.0%
0
   0.0%
1
   1.7%
2
   3.4%
0
   0.0%
4
   0.4%
Black or African American
15
   6.2%
16
   6.6%
17
   6.9%
7
  11.7%
5
   8.6%
3
   4.8%
63
   6.9%
White
165
  68.2%
160
  65.8%
172
  69.6%
45
  75.0%
42
  72.4%
46
  74.2%
630
  69.1%
More than one race
4
   1.7%
1
   0.4%
2
   0.8%
1
   1.7%
2
   3.4%
0
   0.0%
10
   1.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Study Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 242 participants 243 participants 247 participants 60 participants 58 participants 62 participants 912 participants
Main Study
242
 100.0%
243
 100.0%
247
 100.0%
36
  60.0%
33
  56.9%
35
  56.5%
836
  91.7%
Adolescent Substudy
0
   0.0%
0
   0.0%
0
   0.0%
24
  40.0%
25
  43.1%
27
  43.5%
76
   8.3%
Geographic Region  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 242 participants 243 participants 247 participants 60 participants 58 participants 62 participants 912 participants
US/Puerto Rico/Canada
95
  39.3%
95
  39.1%
99
  40.1%
25
  41.7%
24
  41.4%
27
  43.5%
365
  40.0%
Other
147
  60.7%
148
  60.9%
148
  59.9%
35
  58.3%
34
  58.6%
35
  56.5%
547
  60.0%
vIGA-AD   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 242 participants 243 participants 247 participants 60 participants 58 participants 62 participants 912 participants
3 (Moderate)
110
  45.5%
111
  45.7%
111
  44.9%
26
  43.3%
27
  46.6%
29
  46.8%
414
  45.4%
4 (Severe)
132
  54.5%
132
  54.3%
136
  55.1%
34
  56.7%
31
  53.4%
33
  53.2%
498
  54.6%
[1]
Measure Description:

The vIGA-AD was used to assess the severity of AD based on lesion appearance on the following scale:

  • 0-Clear: No inflammatory signs of AD;
  • 1-Almost clear: Barely perceptible erythema, induration/papulation and/or lichenification;
  • 2-Mild: Slight but definite erythema, induration/papulation and/or lichenification. No oozing or crusting;
  • 3-Moderate: Clearly perceptible erythema, induration/papulation and/or lichenification, oozing or crusting may be present;
  • 4-Severe: Marked erythema, induration/papulation and/or lichenification, oozing or crusting may be present.
Eczema Area and Severity Index (EASI) Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 241 participants 243 participants 247 participants 60 participants 58 participants 62 participants 911 participants
28.74  (11.865) 28.65  (11.633) 29.61  (12.030) 30.12  (13.263) 28.01  (12.216) 31.15  (13.998) 29.16  (12.112)
[1]
Measure 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.
[2]
Measure Analysis Population Description: Participants with available data
Disease Duration since Diagnosis   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 242 participants 243 participants 246 participants 60 participants 58 participants 62 participants 911 participants
22.263  (14.0798) 19.802  (13.8089) 21.911  (14.8401) 12.169  (4.7104) 11.184  (4.5479) 12.128  (4.6414) 19.452  (13.4892)
[1]
Measure Analysis Population Description: Participants with available data
1.Primary Outcome
Title Main Study: Percentage of Participants Achieving at Least a 75% Reduction in Eczema Area and Severity Index Score (EASI 75) From Baseline at Week 16
Hide 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.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description

The intent-to-treat population for the main study (ITT_M) includes all participants who were randomized in the main study (adults and adolescents). Non-responder imputation incorporating multiple imputation to handle missing data due to coronavirus disease 2019 pandemic (COVID-19) (NRI-C) was used.

The pre-specified primary analysis included participants enrolled in the main study only; Efficacy analyses of adolescent participants were conducted separately and are reported below.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 278 276 282
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
13.3
(9.3 to 17.3)
60.1
(54.4 to 65.9)
72.9
(67.7 to 78.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 59.6
Confidence Interval (2-Sided) 95%
53.1 to 66.2
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 46.9
Confidence Interval (2-Sided) 95%
39.9 to 53.9
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
2.Primary Outcome
Title Main Study: Percentage of Participants Achieving Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 With a Reduction From Baseline of ≥ 2 Points at Week 16
Hide Description

The vIGA-AD is a validated assessment instrument to rate the severity of atopic dermatitis globally, based on the following scale:

  • 0 - Clear: No inflammatory signs of AD;
  • 1 - Almost clear: Barely perceptible erythema, induration/papulation and/or lichenification, no oozing or crusting;
  • 2 - Mild: Slight but definite erythema, induration/papulation and/or minimal lichenification, no oozing or crusting;
  • 3 - Moderate: Clearly perceptible erythema, induration/papulation and/or lichenification, oozing or crusting may be present;
  • 4 - Severe: Marked erythema, induration/papulation and/or lichenification; Oozing or crusting may be present.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 278 276 282
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
4.7
(2.2 to 7.2)
38.8
(33.0 to 44.5)
52.0
(46.1 to 57.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 47.4
Confidence Interval (2-Sided) 95%
41.0 to 53.7
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 34.0
Confidence Interval (2-Sided) 95%
27.8 to 40.2
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
3.Secondary Outcome
Title Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus Numerical Rating Scale (NRS) at Week 16
Hide Description Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst Pruritus NRS was analyzed based on weekly rolling averages of daily scores.
Time Frame Baseline (last available rolling average before the first dose of study drug) and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study with Worst Pruritus NRS (weekly average) ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 274 270 280
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
9.1
(5.7 to 12.5)
41.9
(36.0 to 47.7)
59.6
(53.9 to 65.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 50.4
Confidence Interval (2-Sided) 95%
43.8 to 57.1
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 32.6
Confidence Interval (2-Sided) 95%
25.8 to 39.4
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
4.Secondary Outcome
Title Main Study: Percentage of Participants Achieving a 90% Reduction From Baseline in EASI Score (EASI 90) at Week 16
Hide 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.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 278 276 282
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
5.4
(2.7 to 8.1)
42.4
(36.6 to 48.2)
58.5
(52.7 to 64.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 53.1
Confidence Interval (2-Sided) 95%
46.7 to 59.4
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 36.9
Confidence Interval (2-Sided) 95%
30.6 to 43.3
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
5.Secondary Outcome
Title Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 4
Hide Description Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst Pruritus NRS was analyzed based on weekly rolling averages of daily scores.
Time Frame Baseline (last available rolling average before the first dose of study drug) and Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study with Worst Pruritus NRS (weekly average) ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 274 270 280
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
3.6
(1.4 to 5.9)
48.9
(42.9 to 54.9)
60.7
(55.0 to 66.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 57.0
Confidence Interval (2-Sided) 95%
50.9 to 63.0
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 45.2
Confidence Interval (2-Sided) 95%
38.9 to 51.4
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
6.Secondary Outcome
Title Main Study: Percentage of Participants Achieving an EASI 75 Response at Week 2
Hide 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.

An EASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in EASI score.
Time Frame Baseline and Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 278 276 282
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
3.6
(1.4 to 5.8)
33.0
(27.4 to 38.5)
44.0
(38.2 to 49.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 40.4
Confidence Interval (2-Sided) 95%
34.2 to 46.5
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 29.4
Confidence Interval (2-Sided) 95%
23.5 to 35.3
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
7.Secondary Outcome
Title Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 1
Hide Description Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst Pruritus NRS was analyzed based on weekly rolling averages of daily scores.
Time Frame Baseline (last available rolling average before the first dose of study drug) and Week 1
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study with Worst Pruritus NRS (weekly average) ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 274 270 280
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.7
(0.0 to 1.7)
7.4
(4.3 to 10.5)
15.7
(11.5 to 20.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 14.9
Confidence Interval (2-Sided) 95%
10.6 to 19.3
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 6.7
Confidence Interval (2-Sided) 95%
3.4 to 10.0
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
8.Secondary Outcome
Title Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Day 2
Hide Description Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11- point scale from 0 (no itch) to 10 (worst imaginable itch). The percentage of participants who had a 4-point or greater improvement from Baseline in Worst Pruritus NRS score at Day 2 was pre-specified as a ranked secondary endpoint for participants in the upadacitinib 30 mg group versus placebo group only.
Time Frame Baseline and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study with Worst Pruritus NRS (daily score) ≥ 4 at Baseline; Non-responder imputation with no special data handling for missing data due to COVID-19 (NRI-NC) was used.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 267 269 278
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.7
(0.0 to 1.8)
7.4
(4.3 to 10.6)
7.9
(4.7 to 11.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 7.2
Confidence Interval (2-Sided) 95%
3.8 to 10.5
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
9.Secondary Outcome
Title Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Day 3
Hide Description

Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).

The percentage of participants who had a 4-point or greater improvement in Worst Pruritus NRS score from Baseline at Day 3 was pre-specified as a ranked secondary endpoint for participants in the upadacitinib 15 mg group versus placebo group only.
Time Frame Baseline and Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study with Worst Pruritus NRS (daily score) ≥ 4 at Baseline; Non-responder imputation with no special data handling for missing data due to COVID-19 (NRI-NC) was used.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 267 269 278
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
3.0
(1.0 to 5.0)
11.5
(7.7 to 15.3)
17.3
(12.8 to 21.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 8.6
Confidence Interval (2-Sided) 95%
4.3 to 12.9
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
10.Secondary Outcome
Title Main Study: Percentage of Participants Experiencing a Flare During the Double-blind Treatment Period
Hide Description A flare, characterized as a clinically meaningful worsening in EASI, is defined as an increase in EASI score of ≥ 6.6 points from Baseline during the double-blind treatment period and prior to use of any rescue medication. Flare was assessed in participants with an EASI score of 65.4 or less at Baseline.
Time Frame From first dose of study drug to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study with an EASI score ≤ 65.4 at Baseline and at least one EASI post-baseline assessment prior to use of rescue medication.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 269 274 277
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
24.5
(19.4 to 29.7)
2.2
(0.5 to 3.9)
1.4
(0.0 to 2.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value -23.1
Confidence Interval (2-Sided) 95%
-28.4 to -17.8
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value -22.4
Confidence Interval (2-Sided) 95%
-27.8 to -16.9
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
11.Secondary Outcome
Title Main Study: Percentage of Participants Achieving a Reduction of ≥ 12 Points From Baseline in Atopic Dermatitis Impact Scale (ADerm-IS) Sleep Domain Score at Week 16
Hide Description

The ADerm-IS is a 10-item patient reported outcome (PRO) questionnaire designed to assess a variety of impacts that participants experience from their AD.

The ADerm-IS sleep domain consists of 3 questions designed to assess the impact of AD on sleep on a daily basis over a 24-hour recall period. The items include difficulty falling asleep, impact on sleep, and waking at night. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The ADerm-IS sleep domain score is the sum of the 3 item scores and ranges from 0 (no impact) to 30 (worst impact). The ADerm-IS sleep domain was analyzed based on weekly rolling averages of daily scores.

The minimal clinically important difference for ADerm-IS sleep domain score is 12.
Time Frame Baseline (last available rolling average before the first dose of study drug) and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study with ADerm-IS Sleep Domain score ≥ 12 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 233 219 228
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
12.4
(8.2 to 16.7)
50.2
(43.6 to 56.9)
62.3
(56.0 to 68.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 49.8
Confidence Interval (2-Sided) 95%
42.2 to 57.3
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 37.9
Confidence Interval (2-Sided) 95%
30.1 to 45.8
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
12.Secondary Outcome
Title Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Atopic Dermatitis Symptom Scale (ADerm-SS) Skin Pain Score at Week 16
Hide Description The ADerm-SS is an 11-item PRO questionnaire designed to assess signs and symptoms that patients may experience due to AD using a 24-hour recall period. For the skin pain item participants were asked on a daily basis to indicate how bad their worst skin pain due to AD was in the past 24 hours on an NRS from 0 (no pain) to 10 (worst imaginable pain). The ADerm-SS skin pain score was analyzed using weekly rolling averages of daily scores. The minimal clinically important difference for ADerm-SS skin pain score is 4.
Time Frame Baseline (last available rolling average before the first dose of study drug) and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study with ADerm-SS Skin Pain Score ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 247 237 238
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
13.4
(9.1 to 17.6)
49.4
(43.0 to 55.7)
65.1
(59.1 to 71.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 51.8
Confidence Interval (2-Sided) 95%
44.4 to 59.1
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 35.9
Confidence Interval (2-Sided) 95%
28.2 to 43.5
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
13.Secondary Outcome
Title Main Study: Percentage of Participants Achieving a Reduction of ≥ 28 Points From Baseline in ADerm-SS 7-Item Total Symptom Score (TSS-7) at Week 16
Hide Description The ADerm-SS is an 11-item questionnaire designed to assess signs and symptoms that participants may experience due to AD using a 24-hour recall period. The 7-item total symptom score includes 7 symptoms (items 1-7 of the ADerm-SS), each assessed on a NRS from 0 (no symptom) to 10 (worst imaginable). The 7 symptoms included in the score are itch while asleep, itch while awake, skin pain (each assessed daily), skin cracking, skin cracking pain, dry skin, and skin flaking (assessed weekly). The TSS-7 score ranges from 0 to 70, with higher scores indicating worsening symptoms. The minimal clinically important difference for ADerm-SS TSS-7 is 28.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study with ADerm-SS TSS-7 ≥ 28 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 244 230 234
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
12.7
(8.5 to 16.9)
53.0
(46.6 to 59.5)
66.2
(60.2 to 72.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 53.3
Confidence Interval (2-Sided) 95%
46.0 to 60.6
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 40.3
Confidence Interval (2-Sided) 95%
32.7 to 48.0
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
14.Secondary Outcome
Title Main Study: Percentage of Participants Achieving a Reduction of ≥ 11 Points From Baseline in ADerm-IS Emotional State Domain Score at Week 16
Hide Description

The ADerm-IS is a 10-item PRO questionnaire designed to assess a variety of impacts that participants experience from their AD.

ADerm-IS emotional state sums three items [Items 8-10] measuring self-consciousness, embarrassment, and sadness with a 7-day recall. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The emotional state domain score ranges from 0 to 30, where higher scores represent worst impact.

The minimal clinically important difference for ADerm-IS emotional state domain score is 11.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study with ADerm-IS Emotional State domain score ≥ 11 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 234 228 228
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
16.7
(11.9 to 21.4)
57.0
(50.6 to 63.4)
71.5
(65.6 to 77.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 54.8
Confidence Interval (2-Sided) 95%
47.2 to 62.3
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 40.3
Confidence Interval (2-Sided) 95%
32.3 to 48.3
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
15.Secondary Outcome
Title Main Study: Percentage of Participants Achieving a Reduction of ≥ 14 Points From Baseline in ADerm-IS Daily Activities Domain Score at Week 16
Hide Description

The ADerm-IS is a 10-item PRO questionnaire designed to assess a variety of impacts that participants experience from their AD.

ADerm-IS Daily Activities sums four items measuring limitations of household, physical, and social activities, and difficulty concentrating with a 7-day recall. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The daily activities domain score ranges from 0 to 40, where higher scores represent worst impact.

The minimal clinically important difference for the ADerm-IS daily activities domain score is 14.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study with ADerm-IS Daily Activities Domain Score ≥ 14 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 227 207 223
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
18.9
(13.8 to 24.0)
57.0
(50.3 to 63.7)
69.5
(63.5 to 75.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 50.6
Confidence Interval (2-Sided) 95%
42.8 to 58.5
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 37.9
Confidence Interval (2-Sided) 95%
29.5 to 46.3
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
16.Secondary Outcome
Title Main Study: Percentage of Participants Achieving a 100% Reduction From Baseline in EASI Score (EASI 100) at Week 16
Hide 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.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 278 276 282
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.7
(0.0 to 1.7)
14.1
(10.0 to 18.2)
18.8
(14.2 to 23.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 18.1
Confidence Interval (2-Sided) 95%
13.5 to 22.7
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 13.4
Confidence Interval (2-Sided) 95%
9.2 to 17.6
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
17.Secondary Outcome
Title Main Study: Percent Change From Baseline in Worst Pruritus NRS at Week 16
Hide Description Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst Pruritus NRS was analyzed based on weekly rolling averages of daily scores. A negative change from Baseline indicates improvement.
Time Frame Baseline (last available rolling average before the first dose of study drug) and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study with non-missing Baseline and Week 16 values; missing data were handled using a mixed-effect model with repeated measurements (MMRM) including observed measurements at all visits, except that measurements after any rescue medication were excluded.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 119 224 235
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change
-17.04
(-22.39 to -11.69)
-51.20
(-55.80 to -46.61)
-66.49
(-71.03 to -61.96)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes only.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Effect Model Repeated Measurement
Comments Mixed-effect model repeat measurement with Baseline, treatment, visit, treatment by visit interaction, Baseline vIGA-AD category and age in the model.
Method of Estimation Estimation Parameter Least Squares (LS) Mean Difference
Estimated Value -49.45
Confidence Interval (2-Sided) 95%
-56.05 to -42.84
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.364
Estimation Comments Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Effect Model Repeated Measurement
Comments Mixed-effect model repeat measurement with Baseline, treatment, visit, treatment by visit interaction, Baseline vIGA-AD category and age in the model.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -34.16
Confidence Interval (2-Sided) 95%
-40.81 to -27.51
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.386
Estimation Comments Difference = Upadacitinib - Placebo
18.Secondary Outcome
Title Main Study: Percent Change From Baseline in EASI Score at Week 16
Hide 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.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study with non-missing Baseline and Week 16 values; missing data were handled using a mixed-effect model with repeated measurements (MMRM) including observed measurements at all visits, except that measurements after any rescue medication were excluded.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 142 246 250
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change
-34.51
(-39.60 to -29.42)
-74.13
(-78.45 to -69.82)
-84.65
(-88.93 to -80.37)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Effect Model Repeated Measurement
Comments Mixed-effect model repeat measurement with Baseline, treatment, visit, treatment by visit interaction, Baseline vIGA-AD category and age in the model.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -50.14
Confidence Interval (2-Sided) 95%
-56.28 to -44.00
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.127
Estimation Comments Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Effect Model Repeated Measurement
Comments Mixed-effect model repeat measurement with Baseline, treatment, visit, treatment by visit interaction, Baseline vIGA-AD category and age in the model.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -39.62
Confidence Interval (2-Sided) 95%
-45.79 to -33.46
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.139
Estimation Comments Difference = Upadacitinib - Placebo
19.Secondary Outcome
Title Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Patient Oriented Eczema Measure (POEM) Total Score at Week 16
Hide Description

The POEM is a 7-item, validated questionnaire used to assess disease symptoms in both children and adults.

Participants respond to 7 questions, including dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping, each scored on a 5-point scale based on frequency of occurrence during the previous week: 0 = no days, 1 = 1 to 2 days, 2 = 3 to 4 days, 3 = 5 to 6 days, and 4 = all days. Item scores are added to provide a total score ranging from 0 (clear) to 28 (very severe atopic eczema). A change in POEM score of 3.4 points is considered the minimal clinically important difference.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study with POEM score ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 268 268 269
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
28.7
(23.3 to 34.1)
70.9
(65.5 to 76.3)
83.5
(79.1 to 88.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 54.7
Confidence Interval (2-Sided) 95%
47.7 to 61.7
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 42.1
Confidence Interval (2-Sided) 95%
34.5 to 49.8
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
20.Secondary Outcome
Title Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Dermatology Life Quality Index (DLQI) at Week 16
Hide Description

The DLQI is a 10-item validated questionnaire used to assess the impact of AD disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. Each item is scored on a 4-point scale (0 = not at all/not relevant; 1 = a little; 2 = a lot; and 3 = very much).

Item scores are added to provide a total score, ranging from 0 to 30, with higher scores indicating greater impairment of QoL.

the DLQI was administered to participants who were ≥ 16 (16 to 75) years old at the time of the Screening visit.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study who were ≥ 16 years old at Screening with DLQI score ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 250 251 251
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
28.4
(22.8 to 34.0)
71.7
(66.1 to 77.3)
77.6
(72.5 to 82.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 49.0
Confidence Interval (2-Sided) 95%
41.4 to 56.5
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only.
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 42.8
Confidence Interval (2-Sided) 95%
35.0 to 50.6
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
21.Secondary Outcome
Title Main Study: Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16
Hide 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.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study with non-missing Baseline and Week 16 values; missing data were handled using a mixed-effect model with repeated measurements (MMRM) including observed measurements at all visits, except that measurements after any rescue medication were excluded.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 136 245 241
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change
-28.43
(-33.34 to -23.52)
-57.90
(-61.84 to -53.97)
-68.44
(-72.44 to -64.44)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Effect Model Repeated Measurement
Comments Mixed-effect model repeat measurement with Baseline, treatment, visit, treatment by visit interaction, Baseline vIGA-AD category and age in the model.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -40.01
Confidence Interval (2-Sided) 95%
-45.80 to -34.22
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.949
Estimation Comments Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Effect Model Repeated Measurement
Comments Mixed-effect model repeat measurement with Baseline, treatment, visit, treatment by visit interaction, Baseline vIGA-AD category and age in the model.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -29.47
Confidence Interval (2-Sided) 95%
-35.24 to -23.69
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.941
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Main Study: Percentage of Participants Achieving a Hospital Anxiety and Depression Scale-Anxiety (HADS-A) Score and Hospital Anxiety and Depression Scale-Depression (HADS-D) Score of < 8 at Week 16
Hide Description The HADS is a 14-item questionnaire, with seven items related to anxiety (HADS-A) and seven items related to depression (HADS-D). Each item is scored from 0 to 3; scores for each subscale range from 0 to 21, with higher scores indicating more distress. For each domain, scores 7 or lower are considered normal, 8 to 10 are borderline, and 11 or higher indicate clinical anxiety or depression.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study with HADS-A ≥ 8 or HADS-D ≥ 8 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 140 137 146
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
11.4
(6.2 to 16.7)
46.0
(37.6 to 54.3)
56.1
(48.1 to 64.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 44.5
Confidence Interval (2-Sided) 95%
35.0 to 54.1
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 34.4
Confidence Interval (2-Sided) 95%
24.7 to 44.2
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
23.Secondary Outcome
Title Main Study: Percentage of Participants Achieving a DLQI Score of 0 or 1 at Week 16
Hide Description

The DLQI is a 10-item validated questionnaire used to assess the impact of AD disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. Each item is scored on a 4-point scale (0 = not at all/not relevant; 1 = a little; 2 = a lot; and 3 = very much).

Item scores are added to provide a total score, ranging from 0 to 30, with higher scores indicating greater impairment of QoL. A score of 0 or 1 means that the disease has no effect at all.

The DLQI was administered to participants who were ≥ 16 (16 to 75) years old at the time of the Screening visit.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for the main study who were ≥ 16 years old at Screening with DLQI score > 1 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Placebo Upadacitinib 15 mg QD Upadacitinib 30 mg QD
Hide Arm/Group Description:
Participants received placebo orally once a day for 16 weeks.
Participants received upadacitinib 15 mg orally once a day for 16 weeks.
Participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 257 252 256
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
4.7
(2.1 to 7.2)
23.8
(18.6 to 29.1)
37.9
(32.0 to 43.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 33.3
Confidence Interval (2-Sided) 95%
26.9 to 39.8
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult])
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 19.1
Confidence Interval (2-Sided) 95%
13.3 to 24.9
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
24.Secondary Outcome
Title Adolescents: Percentage of Participants Achieving an EASI 75 Response at Week 16
Hide 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.

An EASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in EASI score.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population for adolescents (ITT_A) consists of all adolescent participants who were randomized in the main study or the adolescent sub-study. Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Adolescents: Placebo Adolescents: Upadacitinib 15 mg QD Adolescents: Upadacitinib 30 mg QD
Hide Arm/Group Description:
Adolescent participants received placebo orally once a day for 16 weeks.
Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks.
Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 60 58 62
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
13.3
(4.7 to 21.9)
69.0
(57.1 to 80.9)
73.4
(62.3 to 84.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 59.9
Confidence Interval (2-Sided) 95%
45.9 to 73.8
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 55.8
Confidence Interval (2-Sided) 95%
41.1 to 70.4
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
25.Secondary Outcome
Title Adolescents: Percentage of Participants Achieving a vIGA-AD of 0 or 1 With a Reduction From Baseline of ≥ 2 Points at Week 16
Hide Description

The vIGA-AD is a validated assessment instrument to rate the severity of atopic dermatitis globally, based on the following scale:

  • 0 - Clear: No signs of AD;
  • 1 - Almost clear: Barely perceptible erythema, induration/papulation and/or lichenification, no oozing or crusting;;
  • 2 - Mild: Slight but definite erythema, induration/papulation and/or minimal lichenification, no oozing or crusting;
  • 3 - Moderate: Clearly perceptible erythema, induration/papulation and/or lichenification, possible oozing or crusting;
  • 4 - Severe: Marked erythema, induration/papulation and/or lichenification; possible oozing or crusting.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population for adolescents; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Adolescents: Placebo Adolescents: Upadacitinib 15 mg QD Adolescents: Upadacitinib 30 mg QD
Hide Arm/Group Description:
Adolescent participants received placebo orally once a day for 16 weeks.
Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks.
Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 60 58 62
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
5.0
(0.0 to 10.5)
44.8
(32.0 to 57.6)
59.4
(47.0 to 71.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 53.9
Confidence Interval (2-Sided) 95%
40.6 to 67.3
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 39.4
Confidence Interval (2-Sided) 95%
25.7 to 53.1
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
26.Secondary Outcome
Title Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 16
Hide Description Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst pruritus NRS was analyzed based on weekly rolling averages of daily scores.
Time Frame Baseline (last available rolling average before the first dose of study drug) and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for adolescents with Worst Pruritus NRS (weekly average) ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Adolescents: Placebo Adolescents: Upadacitinib 15 mg QD Adolescents: Upadacitinib 30 mg QD
Hide Arm/Group Description:
Adolescent participants received placebo orally once a day for 16 weeks.
Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks.
Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 59 55 60
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
3.4
(0.0 to 8.0)
38.2
(25.3 to 51.0)
56.7
(44.1 to 69.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 53.1
Confidence Interval (2-Sided) 95%
40.0 to 66.1
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 35.0
Confidence Interval (2-Sided) 95%
21.8 to 48.2
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
27.Secondary Outcome
Title Adolescents: Percentage of Participants Achieving an EASI 90 Response at Week 16
Hide 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.

An EASI 90 response is defined as at least a 90% reduction (improvement) from Baseline in EASI score.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for adolescents; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Adolescents: Placebo Adolescents: Upadacitinib 15 mg QD Adolescents: Upadacitinib 30 mg QD
Hide Arm/Group Description:
Adolescent participants received placebo orally once a day for 16 weeks.
Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks.
Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 60 58 62
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
1.7
(0.0 to 4.9)
48.3
(35.4 to 61.1)
62.0
(49.8 to 74.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 60.2
Confidence Interval (2-Sided) 95%
47.5 to 72.9
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 46.7
Confidence Interval (2-Sided) 95%
33.4 to 59.9
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
28.Secondary Outcome
Title Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 4
Hide Description Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst pruritus NRS was analyzed based on weekly rolling averages of daily scores.
Time Frame Baseline (last available rolling average before the first dose of study drug) and Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for adolescents with Worst Pruritus NRS (weekly average) ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Adolescents: Placebo Adolescents: Upadacitinib 15 mg QD Adolescents: Upadacitinib 30 mg QD
Hide Arm/Group Description:
Adolescent participants received placebo orally once a day for 16 weeks.
Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks.
Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 59 55 60
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
3.4
(0.0 to 8.0)
38.2
(25.3 to 51.0)
50.0
(37.3 to 62.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 46.4
Confidence Interval (2-Sided) 95%
33.2 to 59.6
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 34.9
Confidence Interval (2-Sided) 95%
21.4 to 48.4
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
29.Secondary Outcome
Title Adolescents: Percentage of Participants Achieving an EASI 75 Response at Week 2
Hide 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.

An EASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in EASI score.
Time Frame Baseline and Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population for adolescents; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Adolescents: Placebo Adolescents: Upadacitinib 15 mg QD Adolescents: Upadacitinib 30 mg QD
Hide Arm/Group Description:
Adolescent participants received placebo orally once a day for 16 weeks.
Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks.
Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 60 58 62
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
6.7
(0.4 to 13.0)
37.9
(25.4 to 50.4)
53.2
(40.8 to 65.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 46.2
Confidence Interval (2-Sided) 95%
32.4 to 60.0
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 31.3
Confidence Interval (2-Sided) 95%
17.3 to 45.3
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
30.Secondary Outcome
Title Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 1
Hide Description Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst pruritus NRS was analyzed based on weekly rolling averages of daily scores.
Time Frame Baseline (last available rolling average before the first dose of study drug) and Week 1
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for adolescents with Worst Pruritus NRS (weekly average) ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Adolescents: Placebo Adolescents: Upadacitinib 15 mg QD Adolescents: Upadacitinib 30 mg QD
Hide Arm/Group Description:
Adolescent participants received placebo orally once a day for 16 weeks.
Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks.
Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 59 55 60
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.0 [1] 
(NA to NA)
12.7
(3.9 to 21.5)
5.0
(0.0 to 10.5)
[1]
Could not be calculated using the normal approximation to the binomial distribution
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.075
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 5.0
Confidence Interval (2-Sided) 95%
-0.5 to 10.6
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 12.7
Confidence Interval (2-Sided) 95%
3.9 to 21.5
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
31.Secondary Outcome
Title Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Day 2
Hide Description Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).
Time Frame Baseline and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for adolescents with Worst Pruritus NRS (daily score) ≥ 4 at Baseline; Non-responder imputation with no special data handling for missing data due to COVID-19 was used.
Arm/Group Title Adolescents: Placebo Adolescents: Upadacitinib 15 mg QD Adolescents: Upadacitinib 30 mg QD
Hide Arm/Group Description:
Adolescent participants received placebo orally once a day for 16 weeks.
Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks.
Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 59 56 62
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.0 [1] 
(NA to NA)
8.9
(1.5 to 16.4)
3.2
(0.0 to 7.6)
[1]
Could not be calculated using the normal approximation to the binomial distribution
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.151
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 3.2
Confidence Interval (2-Sided) 95%
-1.2 to 7.6
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
32.Secondary Outcome
Title Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Day 3
Hide Description Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).
Time Frame Baseline and Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for adolescents with Worst Pruritus NRS (daily score) ≥ 4 at Baseline; Non-responder imputation with no special data handling for missing data due to COVID-19 was used.
Arm/Group Title Adolescents: Placebo Adolescents: Upadacitinib 15 mg QD Adolescents: Upadacitinib 30 mg QD
Hide Arm/Group Description:
Adolescent participants received placebo orally once a day for 16 weeks.
Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks.
Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 59 56 62
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
1.7
(0.0 to 5.0)
14.3
(5.1 to 23.5)
9.7
(2.3 to 17.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 12.9
Confidence Interval (2-Sided) 95%
3.4 to 22.3
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
33.Secondary Outcome
Title Adolescents: Percentage of Participants Experiencing a Flare During the Double-blind Treatment Period
Hide Description A flare, characterized as a clinically meaningful worsening in EASI, is defined as an increase in EASI score of ≥ 6.6 points from Baseline during the double-blind treatment period and prior to use of any rescue medication. Flares were assessed in participants with an EASI score of 65.4 or less at Baseline.
Time Frame From first dose of study drug to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for adolescents with an EASI score ≤ 65.4 at Baseline and at least one EASI post-baseline assessment prior to use of rescue medication.
Arm/Group Title Adolescents: Placebo Adolescents: Upadacitinib 15 mg QD Adolescents: Upadacitinib 30 mg QD
Hide Arm/Group Description:
Adolescent participants received placebo orally once a day for 16 weeks.
Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks.
Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 60 58 61
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
20.0
(9.9 to 30.1)
1.7
(0.0 to 5.1)
1.6
(0.0 to 4.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value -18.0
Confidence Interval (2-Sided) 95%
-28.0 to -8.0
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value -17.9
Confidence Interval (2-Sided) 95%
-28.1 to -7.7
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
34.Secondary Outcome
Title Adolescents: Percentage of Participants Achieving a Reduction of ≥ 12 Points From Baseline in ADerm-IS Sleep Domain Score at Week 16
Hide Description

The ADerm-IS is a 10-item patient reported outcome questionnaire designed to assess a variety of impacts that participants experience from their AD.

The ADerm-IS sleep domain consists of 3 questions designed to assess the impact of AD on sleep on a daily basis over a 24-hour recall period. The items include difficulty falling asleep, impact on sleep, and waking at night. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The ADerm-IS sleep domain score is the sum of the 3 item scores and ranges from 0 (no impact) to 30 (worst impact). The ADerm-IS sleep domain was analyzed based on weekly rolling averages of daily scores.

The minimal clinically important difference for ADerm-IS sleep domain score is 12.
Time Frame Baseline (last available rolling average before the first dose of study drug) and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for adolescents with ADerm-IS Sleep Domain score ≥ 12 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Adolescents: Placebo Adolescents: Upadacitinib 15 mg QD Adolescents: Upadacitinib 30 mg QD
Hide Arm/Group Description:
Adolescent participants received placebo orally once a day for 16 weeks.
Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks.
Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 42 40 44
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
9.5
(0.6 to 18.4)
37.5
(22.5 to 52.5)
61.4
(47.0 to 75.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 51.5
Confidence Interval (2-Sided) 95%
34.8 to 68.3
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 29.2
Confidence Interval (2-Sided) 95%
11.8 to 46.6
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
35.Secondary Outcome
Title Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in ADerm-SS Skin Pain Score at Week 16
Hide Description

The ADerm-SS is an 11-item PRO questionnaire designed to assess signs and symptoms that patients may experience due to AD using a 24-hour recall period. For the skin pain item participants were asked to indicate on a daily basis how bad their worst skin pain due to AD was in the past 24 hours on an NRS from 0 (no pain) to 10 (worst imaginable pain).

The minimal clinically important difference for ADerm-SS skin pain score is 4. The ADerm-SS skin pain score was analyzed based on weekly rolling averages of daily scores.
Time Frame Baseline (last available rolling average before the first dose of study drug) and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for adolescents with ADerm-SS Skin Pain score ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Adolescents: Placebo Adolescents: Upadacitinib 15 mg QD Adolescents: Upadacitinib 30 mg QD
Hide Arm/Group Description:
Adolescent participants received placebo orally once a day for 16 weeks.
Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks.
Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 53 48 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
7.5
(0.4 to 14.7)
39.6
(25.7 to 53.4)
60.8
(47.4 to 74.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 53.2
Confidence Interval (2-Sided) 95%
38.4 to 68.0
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 31.8
Confidence Interval (2-Sided) 95%
16.5 to 47.1
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
36.Secondary Outcome
Title Adolescents: Percentage of Participants Achieving a Reduction of ≥ 28 Points From Baseline in ADerm-SS TSS-7 at Week 16
Hide Description The ADerm-SS is an 11-item questionnaire designed to assess signs and symptoms that participants may experience due to AD using a 24-hour recall period. The 7-item total symptom score includes 7 symptoms (items 1-7 of the ADerm-SS), each assessed on a NRS from 0 (no symptom) to 10 (worst imaginable). The 7 symptoms included in the score are itch while asleep, itch while awake, skin pain (each assessed daily), skin cracking, skin cracking pain, dry skin, and skin flaking (assessed weekly). The TSS-7 score ranges from 0 to 70, with higher scores indicating worsening symptoms. The minimal clinically important difference for ADerm-SS TSS-7 is 28.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population for adolescents with ADerm-SS TSS-7 ≥ 28 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.
Arm/Group Title Adolescents: Placebo Adolescents: Upadacitinib 15 mg QD Adolescents: Upadacitinib 30 mg QD
Hide Arm/Group Description:
Adolescent participants received placebo orally once a day for 16 weeks.
Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks.
Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Number of Participants Analyzed 55 48 55
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
10.9
(2.7 to 19.1)
47.9
(33.8 to 62.0)
60.0
(47.1 to 72.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 48.9
Confidence Interval (2-Sided) 95%
33.8 to 64.1
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adolescents: Placebo, Adolescents: Upadacitinib 15 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories)
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 37.3
Confidence Interval (2-Sided) 95%
21.1 to 53.6
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
37.Secondary Outcome
Title Adolescents: Percentage of Participants Achieving a Reduction of ≥ 11 Points From Baseline in ADerm-IS Emotional State Domain Score at Week 16
Hide Description

The ADerm-IS is a 10-item PRO questionnaire designed to assess a variety of impacts that participants experience from their AD.

ADerm-IS emotional state sums three items [Items 8-10] measuring self-consciousness, embarrassment, and sadness with a 7-day recall. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The emotional state domain score ranges from 0 to 30, where higher scores represent worst impact.

The minimal clinically important difference for ADerm-IS emotional state domain score is 11.