Trial Outcomes & Findings for A Study to Compare Safety and Efficacy of Upadacitinib to Dupilumab in Adult Participants With Moderate to Severe Atopic Dermatitis (NCT NCT03738397)

Last Updated: 2024-03-15

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

673 participants

Primary outcome timeframe

Baseline and Week 16

Results posted on

2024-03-15

Participant Flow

Participants were randomized at 128 sites located in 22 countries (Australia, Canada, Croatia, Czechia, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Malaysia, Netherlands, New Zealand, Norway, Poland, Singapore, Spain, Taiwan, Ukraine, United Kingdom, and the United States).

Participants were randomly assigned in a 1:1 ratio to receive upadacitinib or dupilumab. Randomization was stratified by disease severity (Validated Investigator Global Assessment Scale for Atopic Dermatitis \[vIGA-AD\] moderate \[3\] vs severe \[4\]) and age (\<40, ≥ 40 to \< 65, ≥ 65 years).

Participant milestones

Participant milestones
Measure	Dupilumab 300 mg EOW Participants received a loading dose of 600 mg dupilumab by subcutaneous (SC) injection on Day 1 followed by 300 mg dupilumab SC every other week (EOW) until Week 22 and placebo to upadacitinib orally once a day (QD) up to Week 24.	Upadacitinib 30 mg QD Participants received 30 mg upadacitinib orally once a day up to Week 24 and placebo to dupilumab SC EOW up to Week 22.
Overall Study STARTED	331	342
Overall Study COMPLETED	308	312
Overall Study NOT COMPLETED	23	30

Reasons for withdrawal

Reasons for withdrawal
Measure	Dupilumab 300 mg EOW Participants received a loading dose of 600 mg dupilumab by subcutaneous (SC) injection on Day 1 followed by 300 mg dupilumab SC every other week (EOW) until Week 22 and placebo to upadacitinib orally once a day (QD) up to Week 24.	Upadacitinib 30 mg QD Participants received 30 mg upadacitinib orally once a day up to Week 24 and placebo to dupilumab SC EOW up to Week 22.
Overall Study Adverse Event	3	7
Overall Study Withdrawal by Subject	8	11
Overall Study Lost to Follow-up	7	5
Overall Study COVID-19 Logistical Restrictions	1	1
Overall Study Other	4	6

Baseline Characteristics

A Study to Compare Safety and Efficacy of Upadacitinib to Dupilumab in Adult Participants With Moderate to Severe Atopic Dermatitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dupilumab 300 mg EOW n=331 Participants Participants received a loading dose of 600 mg dupilumab by SC injection on Day 1 followed by 300 mg dupilumab SC EOW until Week 22 and placebo to upadacitinib orally QD up to Week 24.	Upadacitinib 30 mg QD n=342 Participants Participants received 30 mg upadacitinib orally once a day up to Week 24 and placebo to dupilumab SC EOW up to Week 22.	Total n=673 Participants Total of all reporting groups
Age, Continuous	36.3 years STANDARD_DEVIATION 13.81 • n=5 Participants	36.2 years STANDARD_DEVIATION 14.42 • n=7 Participants	36.3 years STANDARD_DEVIATION 14.11 • n=5 Participants
Age, Customized < 40 years	223 Participants n=5 Participants	228 Participants n=7 Participants	451 Participants n=5 Participants
Age, Customized ≥ 40 to < 65 years	94 Participants n=5 Participants	98 Participants n=7 Participants	192 Participants n=5 Participants
Age, Customized ≥ 65 years	14 Participants n=5 Participants	16 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Female	139 Participants n=5 Participants	159 Participants n=7 Participants	298 Participants n=5 Participants
Sex: Female, Male Male	192 Participants n=5 Participants	183 Participants n=7 Participants	375 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	31 Participants n=5 Participants	25 Participants n=7 Participants	56 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	300 Participants n=5 Participants	317 Participants n=7 Participants	617 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	231 Participants n=5 Participants	229 Participants n=7 Participants	460 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	15 Participants n=5 Participants	25 Participants n=7 Participants	40 Participants n=5 Participants
Race/Ethnicity, Customized Asian	78 Participants n=5 Participants	77 Participants n=7 Participants	155 Participants n=5 Participants
Race/Ethnicity, Customized American Indian/Alaska Native	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Disease Severity 3 (Moderate)	159 Participants n=5 Participants	169 Participants n=7 Participants	328 Participants n=5 Participants
Disease Severity 4 (Severe)	172 Participants n=5 Participants	173 Participants n=7 Participants	345 Participants n=5 Participants
Eczema Area and Severity Index (EASI) Score	29.21 score on a scale STANDARD_DEVIATION 11.551 • n=5 Participants	30.96 score on a scale STANDARD_DEVIATION 12.550 • n=7 Participants	30.10 score on a scale STANDARD_DEVIATION 12.092 • n=5 Participants
Duration Since AD Diagnosis	25.474 years STANDARD_DEVIATION 14.8251 • n=5 Participants	23.608 years STANDARD_DEVIATION 14.7697 • n=7 Participants	24.526 years STANDARD_DEVIATION 14.8154 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

Outcome measures

Outcome measures
Measure	Dupilumab 300 mg EOW n=331 Participants Participants received a loading dose of 600 mg dupilumab by SC injection on Day 1 followed by 300 mg dupilumab SC EOW until Week 22 and placebo to upadacitinib orally QD up to Week 24.	Upadacitinib 30 mg QD n=342 Participants Participants received 30 mg upadacitinib orally once a day up to Week 24 and placebo to dupilumab SC EOW up to Week 22.
Percentage of Participants Achieving a 75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 75) at Week 16	62.6 percentage of participants Interval 57.4 to 67.8	72.4 percentage of participants Interval 67.6 to 77.2

SECONDARY outcome

Timeframe: Baseline (Week 0) to Week 16

Population: Intent-to-treat population with non-missing Baseline and at least one post-baseline value; 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.

The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). The percent change from Baseline was calculated from a rolling weekly average; a negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Dupilumab 300 mg EOW n=239 Participants Participants received a loading dose of 600 mg dupilumab by SC injection on Day 1 followed by 300 mg dupilumab SC EOW until Week 22 and placebo to upadacitinib orally QD up to Week 24.	Upadacitinib 30 mg QD n=252 Participants Participants received 30 mg upadacitinib orally once a day up to Week 24 and placebo to dupilumab SC EOW up to Week 22.
Percent Change From Baseline in Worst Pruritus Numerical Rating Scale (NRS) Score at Week 16	-49.58 percent change Standard Error 1.986	-67.78 percent change Standard Error 1.906

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

Outcome measures

Outcome measures
Measure	Dupilumab 300 mg EOW n=331 Participants Participants received a loading dose of 600 mg dupilumab by SC injection on Day 1 followed by 300 mg dupilumab SC EOW until Week 22 and placebo to upadacitinib orally QD up to Week 24.	Upadacitinib 30 mg QD n=342 Participants Participants received 30 mg upadacitinib orally once a day up to Week 24 and placebo to dupilumab SC EOW up to Week 22.
Percentage of Participants Achieving a 100% Reduction From Baseline in EASI Score (EASI 100) at Week 16	7.9 percentage of participants Interval 5.0 to 10.8	28.4 percentage of participants Interval 23.6 to 33.2

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

Outcome measures

Outcome measures
Measure	Dupilumab 300 mg EOW n=331 Participants Participants received a loading dose of 600 mg dupilumab by SC injection on Day 1 followed by 300 mg dupilumab SC EOW until Week 22 and placebo to upadacitinib orally QD up to Week 24.	Upadacitinib 30 mg QD n=342 Participants Participants received 30 mg upadacitinib orally once a day up to Week 24 and placebo to dupilumab SC EOW up to Week 22.
Percentage of Participants Achieving a 90% Reduction From Baseline in EASI Score (EASI 90) at Week 16	40.3 percentage of participants Interval 35.0 to 45.6	61.6 percentage of participants Interval 56.4 to 66.8

SECONDARY outcome

Timeframe: Baseline (Week 0) to Week 4

Outcome measures

Outcome measures
Measure	Dupilumab 300 mg EOW n=297 Participants Participants received a loading dose of 600 mg dupilumab by SC injection on Day 1 followed by 300 mg dupilumab SC EOW until Week 22 and placebo to upadacitinib orally QD up to Week 24.	Upadacitinib 30 mg QD n=327 Participants Participants received 30 mg upadacitinib orally once a day up to Week 24 and placebo to dupilumab SC EOW up to Week 22.
Percent Change From Baseline in Worst Pruritus Numerical Rating Scale (NRS) Score at Week 4	-32.39 percent change Standard Error 2.288	-60.41 percent change Standard Error 2.204

SECONDARY outcome

Timeframe: Baseline and Week 2

Population: Intent-to-treat population; Non-responder imputation while incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

Outcome measures

Outcome measures
Measure	Dupilumab 300 mg EOW n=331 Participants Participants received a loading dose of 600 mg dupilumab by SC injection on Day 1 followed by 300 mg dupilumab SC EOW until Week 22 and placebo to upadacitinib orally QD up to Week 24.	Upadacitinib 30 mg QD n=342 Participants Participants received 30 mg upadacitinib orally once a day up to Week 24 and placebo to dupilumab SC EOW up to Week 22.
Percentage of Participants Achieving a 75% Reduction From Baseline in EASI Score at Week 2	18.2 percentage of participants Interval 14.0 to 22.4	44.3 percentage of participants Interval 39.1 to 49.6

SECONDARY outcome

Timeframe: Baseline (Week 0) to Week 1

Outcome measures

Outcome measures
Measure	Dupilumab 300 mg EOW n=314 Participants Participants received a loading dose of 600 mg dupilumab by SC injection on Day 1 followed by 300 mg dupilumab SC EOW until Week 22 and placebo to upadacitinib orally QD up to Week 24.	Upadacitinib 30 mg QD n=331 Participants Participants received 30 mg upadacitinib orally once a day up to Week 24 and placebo to dupilumab SC EOW up to Week 22.
Percent Change From Baseline in Worst Pruritus Numerical Rating Scale (NRS) Score at Week 1	-8.94 percent change Standard Error 1.831	-31.96 percent change Standard Error 1.772

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population with Worst Pruritus NRS ≥ 4 at Baseline; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

Outcome measures

Outcome measures
Measure	Dupilumab 300 mg EOW n=323 Participants Participants received a loading dose of 600 mg dupilumab by SC injection on Day 1 followed by 300 mg dupilumab SC EOW until Week 22 and placebo to upadacitinib orally QD up to Week 24.	Upadacitinib 30 mg QD n=334 Participants Participants received 30 mg upadacitinib orally once a day up to Week 24 and placebo to dupilumab SC EOW up to Week 22.
Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 16	36.4 percentage of participants Interval 31.1 to 41.6	56.1 percentage of participants Interval 50.8 to 61.5

Adverse Events

Dupilumab 300 mg EOW

Serious events: 7 serious events

Other events: 134 other events

Deaths: 0 deaths

Upadacitinib 30 mg QD

Serious events: 14 serious events

Other events: 167 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Dupilumab 300 mg EOW n=331 participants at risk Participants received a loading dose of 600 mg dupilumab by SC injection on Day 1 followed by 300 mg dupilumab SC EOW until Week 22 and placebo to upadacitinib orally QD up to Week 24.	Upadacitinib 30 mg QD n=342 participants at risk Participants received 30 mg upadacitinib orally once a day up to Week 24 and placebo to dupilumab SC EOW up to Week 22.
Infections and infestations CONJUNCTIVITIS	10.6% 35/331 • Number of events 36 • All-cause mortality was recorded from Day 1 up to 12 weeks after last injection (34 weeks). Treatment-emergent adverse events are from first dose of upadacitinib/dupilumab through 30 days following the last dose of upadacitinib or 84 days following the last dose of dupilumab (up to 34 weeks).	1.5% 5/342 • Number of events 6 • All-cause mortality was recorded from Day 1 up to 12 weeks after last injection (34 weeks). Treatment-emergent adverse events are from first dose of upadacitinib/dupilumab through 30 days following the last dose of upadacitinib or 84 days following the last dose of dupilumab (up to 34 weeks).
Infections and infestations FOLLICULITIS	1.2% 4/331 • Number of events 4 • All-cause mortality was recorded from Day 1 up to 12 weeks after last injection (34 weeks). Treatment-emergent adverse events are from first dose of upadacitinib/dupilumab through 30 days following the last dose of upadacitinib or 84 days following the last dose of dupilumab (up to 34 weeks).	6.4% 22/342 • Number of events 22 • All-cause mortality was recorded from Day 1 up to 12 weeks after last injection (34 weeks). Treatment-emergent adverse events are from first dose of upadacitinib/dupilumab through 30 days following the last dose of upadacitinib or 84 days following the last dose of dupilumab (up to 34 weeks).
Infections and infestations NASOPHARYNGITIS	8.2% 27/331 • Number of events 31 • All-cause mortality was recorded from Day 1 up to 12 weeks after last injection (34 weeks). Treatment-emergent adverse events are from first dose of upadacitinib/dupilumab through 30 days following the last dose of upadacitinib or 84 days following the last dose of dupilumab (up to 34 weeks).	6.7% 23/342 • Number of events 33 • All-cause mortality was recorded from Day 1 up to 12 weeks after last injection (34 weeks). Treatment-emergent adverse events are from first dose of upadacitinib/dupilumab through 30 days following the last dose of upadacitinib or 84 days following the last dose of dupilumab (up to 34 weeks).
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	5.1% 17/331 • Number of events 20 • All-cause mortality was recorded from Day 1 up to 12 weeks after last injection (34 weeks). Treatment-emergent adverse events are from first dose of upadacitinib/dupilumab through 30 days following the last dose of upadacitinib or 84 days following the last dose of dupilumab (up to 34 weeks).	7.6% 26/342 • Number of events 26 • All-cause mortality was recorded from Day 1 up to 12 weeks after last injection (34 weeks). Treatment-emergent adverse events are from first dose of upadacitinib/dupilumab through 30 days following the last dose of upadacitinib or 84 days following the last dose of dupilumab (up to 34 weeks).
Infections and infestations URINARY TRACT INFECTION	4.5% 15/331 • Number of events 16 • All-cause mortality was recorded from Day 1 up to 12 weeks after last injection (34 weeks). Treatment-emergent adverse events are from first dose of upadacitinib/dupilumab through 30 days following the last dose of upadacitinib or 84 days following the last dose of dupilumab (up to 34 weeks).	5.3% 18/342 • Number of events 19 • All-cause mortality was recorded from Day 1 up to 12 weeks after last injection (34 weeks). Treatment-emergent adverse events are from first dose of upadacitinib/dupilumab through 30 days following the last dose of upadacitinib or 84 days following the last dose of dupilumab (up to 34 weeks).
Investigations BLOOD CREATINE PHOSPHOKINASE INCREASED	3.0% 10/331 • Number of events 12 • All-cause mortality was recorded from Day 1 up to 12 weeks after last injection (34 weeks). Treatment-emergent adverse events are from first dose of upadacitinib/dupilumab through 30 days following the last dose of upadacitinib or 84 days following the last dose of dupilumab (up to 34 weeks).	7.6% 26/342 • Number of events 27 • All-cause mortality was recorded from Day 1 up to 12 weeks after last injection (34 weeks). Treatment-emergent adverse events are from first dose of upadacitinib/dupilumab through 30 days following the last dose of upadacitinib or 84 days following the last dose of dupilumab (up to 34 weeks).
Nervous system disorders HEADACHE	7.3% 24/331 • Number of events 32 • All-cause mortality was recorded from Day 1 up to 12 weeks after last injection (34 weeks). Treatment-emergent adverse events are from first dose of upadacitinib/dupilumab through 30 days following the last dose of upadacitinib or 84 days following the last dose of dupilumab (up to 34 weeks).	5.0% 17/342 • Number of events 22 • All-cause mortality was recorded from Day 1 up to 12 weeks after last injection (34 weeks). Treatment-emergent adverse events are from first dose of upadacitinib/dupilumab through 30 days following the last dose of upadacitinib or 84 days following the last dose of dupilumab (up to 34 weeks).
Skin and subcutaneous tissue disorders ACNE	3.3% 11/331 • Number of events 12 • All-cause mortality was recorded from Day 1 up to 12 weeks after last injection (34 weeks). Treatment-emergent adverse events are from first dose of upadacitinib/dupilumab through 30 days following the last dose of upadacitinib or 84 days following the last dose of dupilumab (up to 34 weeks).	18.7% 64/342 • Number of events 72 • All-cause mortality was recorded from Day 1 up to 12 weeks after last injection (34 weeks). Treatment-emergent adverse events are from first dose of upadacitinib/dupilumab through 30 days following the last dose of upadacitinib or 84 days following the last dose of dupilumab (up to 34 weeks).
Skin and subcutaneous tissue disorders DERMATITIS ATOPIC	9.7% 32/331 • Number of events 51 • All-cause mortality was recorded from Day 1 up to 12 weeks after last injection (34 weeks). Treatment-emergent adverse events are from first dose of upadacitinib/dupilumab through 30 days following the last dose of upadacitinib or 84 days following the last dose of dupilumab (up to 34 weeks).	10.5% 36/342 • Number of events 52 • All-cause mortality was recorded from Day 1 up to 12 weeks after last injection (34 weeks). Treatment-emergent adverse events are from first dose of upadacitinib/dupilumab through 30 days following the last dose of upadacitinib or 84 days following the last dose of dupilumab (up to 34 weeks).
Infections and infestations ORAL HERPES	2.7% 9/331 • Number of events 10 • All-cause mortality was recorded from Day 1 up to 12 weeks after last injection (34 weeks). Treatment-emergent adverse events are from first dose of upadacitinib/dupilumab through 30 days following the last dose of upadacitinib or 84 days following the last dose of dupilumab (up to 34 weeks).	5.0% 17/342 • Number of events 21 • All-cause mortality was recorded from Day 1 up to 12 weeks after last injection (34 weeks). Treatment-emergent adverse events are from first dose of upadacitinib/dupilumab through 30 days following the last dose of upadacitinib or 84 days following the last dose of dupilumab (up to 34 weeks).

Additional Information

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