Trial Outcomes & Findings for Open-label Study of Dupilumab in Patients With Atopic Dermatitis (NCT NCT01949311)

NCT ID: NCT01949311

Last Updated: 2023-10-17

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2733 participants

Primary outcome timeframe

Up to 272 weeks

Results posted on

2023-10-17

Participant Flow

A total of 1297 participants completed the study and 1380 participants had withdrawn. Withdrawal from study included study terminated by the Sponsor (708), and withdrawal by the participant (375), Adverse Event (107), Lost to Follow-Up (73), Lack of Efficacy (50), Protocol Deviation (34), Pregnancy (20), Physician Decision (9), and reasons not specified (4)

Participant milestones

Participant milestones
Measure	Dupilumab Participants received repeated doses of dupilumab
Overall Study STARTED	2677
Overall Study COMPLETED	1297
Overall Study NOT COMPLETED	1380

Reasons for withdrawal

Reasons for withdrawal
Measure	Dupilumab Participants received repeated doses of dupilumab
Overall Study Lost to Follow-up	73
Overall Study Terminated by Sponsor	708
Overall Study Withdrawal by Subject	375
Overall Study Lack of Efficacy	50
Overall Study Protocol Deviation	34
Overall Study Pregnancy	20
Overall Study Physician Decision	9
Overall Study Other	4
Overall Study Adverse Event	107

Baseline Characteristics

Open-label Study of Dupilumab in Patients With Atopic Dermatitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Age, Continuous	39.2 Years STANDARD_DEVIATION 13.42 • n=5 Participants
Sex: Female, Male Female	1066 Participants n=5 Participants
Sex: Female, Male Male	1611 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	94 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2532 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	51 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	541 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	147 Participants n=5 Participants
Race (NIH/OMB) White	1936 Participants n=5 Participants
Race (NIH/OMB) More than one race	33 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	20 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 272 weeks

Population: The safety analysis set (SAF) will include all patients who received any study drug; it is based on the treatment received (as treated).

Outcome measures

Outcome measures
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Number of Treatment Emergent Adverse Events (TEAEs)	14717 Number of Events

PRIMARY outcome

Timeframe: Up to 24 Weeks

Population: The sub-study SAF includes all patients who receive new dupilumab drug product in the sub-study.

Adverse events of special interest in this study include: Anaphylactic reactions, Systemic hypersensitivity reactions, Helminthic infections, Any severe type of conjunctivitis or blepharitis, Keratitis, Clinically symptomatic eosinophilia (or eosinophilia associated with clinical symptoms)

Outcome measures

Outcome measures
Measure	Dupilumab n=50 Participants Participants received repeated doses of dupilumab
OPTIONAL SUB-STUDY: Number of Adverse Events of Special Interest (AESIs) Through the Last Study Visit After Switching to the New Dupilumab Drug Product	0 Events

SECONDARY outcome

Timeframe: Up to 272 weeks

Population: The safety analysis set (SAF) will include all patients who received any study drug; it is based on the treatment received (as treated).

Outcome measures

Outcome measures
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Number of Serious Adverse Events (SAEs) of Special Interest	9 Events

SECONDARY outcome

Timeframe: Up to 272 weeks

Population: The safety analysis set (SAF) will include all patients who received any study drug; it is based on the treatment received (as treated).

Rate (events per patient-year) of AESIs Adverse events of special interest in this study include: Anaphylactic reactions, Systemic hypersensitivity reactions, Helminthic infections, Any severe type of conjunctivitis or blepharitis, Keratitis, Clinically symptomatic eosinophilia (or eosinophilia associated with clinical symptoms)

Outcome measures

Outcome measures
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Rate of AESIs	2.762 Events per Patient-Year

SECONDARY outcome

Timeframe: Up to 272 weeks

Population: The safety analysis set (SAF) will include all patients who received any study drug; it is based on the treatment received (as treated).

Outcome measures

Outcome measures
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Number of AESIs	161 Events

SECONDARY outcome

Timeframe: Up to 272 weeks (End of Study), "Baseline, Weeks 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 272 (End of Study)

Population: The safety analysis set (SAF) will include all patients who received any study drug; it is based on the treatment received (as treated).

IGA is an assessment scale used to determine severity of hand and foot AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration.

Outcome measures

Outcome measures
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit Baseline of study	12.0 Percentage of Participants
Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit Week 4	31.1 Percentage of Participants
Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit Week 16	46.7 Percentage of Participants
Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit Week 36	46.2 Percentage of Participants
Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit Week 52	53.8 Percentage of Participants
Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit Week 100	58.2 Percentage of Participants
Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit Week 124	59.6 Percentage of Participants
Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit Week 156	67.2 Percentage of Participants
Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit Week 172	71.1 Percentage of Participants
Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit Week 188	56.5 Percentage of Participants
Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit Week 204	64.4 Percentage of Participants
Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit Week 220	81.2 Percentage of Participants
Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit Week 236	50.0 Percentage of Participants
Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit End of Study (Extension)	67.5 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 272 weeks (End of Study), "Baseline, Weeks 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 272 (End of Study)"

Population: The safety analysis set (SAF) will include all patients who received any study drug; it is based on the treatment received (as treated). Here 'n' = number of evaluable participants at the specified timeframe

The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, induration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD.

Outcome measures

Outcome measures
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Baseline of study	33.4 Percentage of Participants
Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 4	65.3 Percentage of Participants
Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 16	82.0 Percentage of Participants
Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 36	85.3 Percentage of Participants
Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 52	88.8 Percentage of Participants
Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 100	91.4 Percentage of Participants
Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 124	92.0 Percentage of Participants
Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 156	89.5 Percentage of Participants
Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 172	94.1 Percentage of Participants
Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 188	96.8 Percentage of Participants
Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 204	90.9 Percentage of Participants
Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 220	93.5 Percentage of Participants
Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 236	100 Percentage of Participants
Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit End of Study (Extension)	88.9 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 272 weeks (End of Study), "Baseline, Weeks 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 272 (End of Study)"

Low disease activity state is defined as an IGA score of ≤2 \[mild = 2, almost clear = 1, or clear = 0\]

Outcome measures

Outcome measures
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit Baseline of study	34.7 Percentage of Participants
Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit Week 4	70.0 Percentage of Participants
Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit Week 16	83.0 Percentage of Participants
Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit Week 36	84.6 Percentage of Participants
Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit Week 52	89.6 Percentage of Participants
Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit Week 100	90.9 Percentage of Participants
Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit Week 124	93.1 Percentage of Participants
Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit Week 156	94.8 Percentage of Participants
Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit Week 172	96.3 Percentage of Participants
Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit Week 188	96.8 Percentage of Participants
Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit Week 204	96.0 Percentage of Participants
Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit Week 220	97.1 Percentage of Participants
Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit Week 236	90.0 Percentage of Participants
Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit End of Study (Extension)	92.6 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 272 weeks (End of Study), "Baseline, Weeks 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 272 (End of Study)"

Outcome measures

Outcome measures
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Change From Baseline in EASI Score at Each Visit Week 4	-8.59 Score on a scale Standard Deviation 10.196
Change From Baseline in EASI Score at Each Visit Week 16	-11.89 Score on a scale Standard Deviation 12.583
Change From Baseline in EASI Score at Each Visit Week 36	-17.32 Score on a scale Standard Deviation 13.989
Change From Baseline in EASI Score at Each Visit Week 52	-16.46 Score on a scale Standard Deviation 13.719
Change From Baseline in EASI Score at Each Visit Week 100	-17.99 Score on a scale Standard Deviation 14.049
Change From Baseline in EASI Score at Each Visit Week 124	-17.68 Score on a scale Standard Deviation 13.794
Change From Baseline in EASI Score at Each Visit Week 156	-14.23 Score on a scale Standard Deviation 14.358
Change From Baseline in EASI Score at Each Visit Week 172	-13.23 Score on a scale Standard Deviation 13.651
Change From Baseline in EASI Score at Each Visit Week 188	-19.24 Score on a scale Standard Deviation 11.253
Change From Baseline in EASI Score at Each Visit Week 204	-14.50 Score on a scale Standard Deviation 15.615
Change From Baseline in EASI Score at Each Visit Week 220	-12.75 Score on a scale Standard Deviation 14.444
Change From Baseline in EASI Score at Each Visit Week 236	-16.69 Score on a scale Standard Deviation 9.743
Change From Baseline in EASI Score at Each Visit End of Study (Extension)	-13.14 Score on a scale Standard Deviation 14.614

SECONDARY outcome

Timeframe: Up to 272 weeks (End of Study), "Baseline, Weeks 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 272 (End of Study)"

The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score range from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD.

Outcome measures

Outcome measures
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Percent Change From Baseline in EASI Score at Each Visit Week 4	-42.02 Percent of Change Standard Deviation 88.963
Percent Change From Baseline in EASI Score at Each Visit Week 16	-54.82 Percent of Change Standard Deviation 316.630
Percent Change From Baseline in EASI Score at Each Visit Week 36	-60.40 Percent of Change Standard Deviation 603.886
Percent Change From Baseline in EASI Score at Each Visit Week 52	-75.76 Percent of Change Standard Deviation 73.014
Percent Change From Baseline in EASI Score at Each Visit Week 100	-82.61 Percent of Change Standard Deviation 29.534
Percent Change From Baseline in EASI Score at Each Visit Week 124	-84.15 Percent of Change Standard Deviation 27.737
Percent Change From Baseline in EASI Score at Each Visit Week 156	-83.45 Percent of Change Standard Deviation 32.410
Percent Change From Baseline in EASI Score at Each Visit Week 172	-74.98 Percent of Change Standard Deviation 78.138
Percent Change From Baseline in EASI Score at Each Visit Week 188	-88.72 Percent of Change Standard Deviation 15.122
Percent Change From Baseline in EASI Score at Each Visit Week 204	-70.91 Percent of Change Standard Deviation 74.941
Percent Change From Baseline in EASI Score at Each Visit Week 220	-30.79 Percent of Change Standard Deviation 370.994
Percent Change From Baseline in EASI Score at Each Visit Week 236	-87.56 Percent of Change Standard Deviation 10.851
Percent Change From Baseline in EASI Score at Each Visit End of Study (Extension)	-55.44 Percent of Change Standard Deviation 213.819

SECONDARY outcome

Timeframe: Up to 272 weeks (End of Study), "Baseline, Weeks 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 272 (End of Study)"

EASI-50 was defined as \>=50% reduction in EASI scores from baseline of the parent study

Outcome measures

Outcome measures
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 4	86.0 Percentage of Participants
Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 16	95.0 Percentage of Participants
Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 36	96.7 Percentage of Participants
Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 52	97.4 Percentage of Participants
Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 100	98.5 Percentage of Participants
Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 124	98.3 Percentage of Participants
Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 156	97.4 Percentage of Participants
Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 172	98.4 Percentage of Participants
Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 188	100 Percentage of Participants
Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 204	94.9 Percentage of Participants
Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 220	97.8 Percentage of Participants
Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 236	100 Percentage of Participants
Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit End of Study (Extension)	96.9 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 272 weeks (End of Study), "Baseline, Weeks 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 272 (End of Study)"

EASI-90 was defined as \>=90% reduction in EASI scores from baseline of the parent study

Outcome measures

Outcome measures
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 4	38.6 Percentage of Participants
Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 16	57.7 Percentage of Participants
Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 36	59.7 Percentage of Participants
Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 52	68.4 Percentage of Participants
Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 100	73.0 Percentage of Participants
Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 124	74.4 Percentage of Participants
Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 156	76.3 Percentage of Participants
Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 172	81.8 Percentage of Participants
Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 188	72.6 Percentage of Participants
Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 204	75.8 Percentage of Participants
Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 220	84.1 Percentage of Participants
Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit Week 236	70.0 Percentage of Participants
Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit End of Study (Extension)	76.2 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 272 weeks (End of Study), "Baseline, Weeks 1, 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 252, 272 (End of Study)"

Population: The safety analysis set (SAF) includes all patients who received any study drug; it is based on the treatment received. Participants recorded Pruritus score using IVRS (Interactive Voice Recording System) at specified timepoints

The Pruritus NRS is an assessment tool for patients to report the intensity of their pruritus (itch), using a scale from 0-10, where 0 is no itch and 10 is the worst itch imaginable. Daily peak pruritus NRS score is the worst one between morning and evening scores of the day. Baseline Pruritus NRS is determined based on average of daily peak NRS scores during the 7 days immediately preceding randomization. A minimum of 4 daily scores out of 7 days is required to calculate baseline average score. Weekly worst score is calculated by taking the worst score within the week

Outcome measures

Outcome measures
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study Week 1	-2.86 Score on a Scale Standard Deviation 2.492
Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study Week 4	-3.81 Score on a Scale Standard Deviation 2.403
Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study Week 16	-4.44 Score on a Scale Standard Deviation 2.377
Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study Week 36	-4.67 Score on a Scale Standard Deviation 2.365
Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study Week 52	-4.76 Score on a Scale Standard Deviation 2.371
Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study Week 100	-4.69 Score on a Scale Standard Deviation 2.315
Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study Week 124	-4.56 Score on a Scale Standard Deviation 2.359
Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study Week 156	-4.37 Score on a Scale Standard Deviation 2.352
Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study Week 172	-4.64 Score on a Scale Standard Deviation 2.256
Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study Week 188	-4.73 Score on a Scale Standard Deviation 2.194
Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study Week 204	-4.83 Score on a Scale Standard Deviation 2.341
Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study Week 220	-4.90 Score on a Scale Standard Deviation 2.231
Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study Week 236	-4.81 Score on a Scale Standard Deviation 2.308
Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study Week 252	-4.89 Score on a Scale Standard Deviation 2.201
Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study Week 272	-4.69 Score on a Scale Standard Deviation 2.238

SECONDARY outcome

Timeframe: Up to 272 weeks (End of Study), "Baseline, Weeks 1, 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 252, 272 (End of Study)"

Outcome measures

Outcome measures
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Percent Change From Baseline in Pruritus NRS Week 1	-9.55 Percent Change Standard Deviation 40.989
Percent Change From Baseline in Pruritus NRS Week 4	-28.88 Percent Change Standard Deviation 41.792
Percent Change From Baseline in Pruritus NRS Week 16	-38.96 Percent Change Standard Deviation 47.891
Percent Change From Baseline in Pruritus NRS Week 36	-41.38 Percent Change Standard Deviation 52.300
Percent Change From Baseline in Pruritus NRS Week 52	-46.41 Percent Change Standard Deviation 41.912
Percent Change From Baseline in Pruritus NRS Week 100	-50.62 Percent Change Standard Deviation 42.112
Percent Change From Baseline in Pruritus NRS Week 124	-51.47 Percent Change Standard Deviation 39.063
Percent Change From Baseline in Pruritus NRS Week 156	-48.16 Percent Change Standard Deviation 55.076
Percent Change From Baseline in Pruritus NRS Week 172	-50.30 Percent Change Standard Deviation 42.907
Percent Change From Baseline in Pruritus NRS Week 188	-50.56 Percent Change Standard Deviation 43.444
Percent Change From Baseline in Pruritus NRS Week 204	-52.53 Percent Change Standard Deviation 43.465
Percent Change From Baseline in Pruritus NRS Week 220	-51.18 Percent Change Standard Deviation 39.244
Percent Change From Baseline in Pruritus NRS Week 236	-51.67 Percent Change Standard Deviation 37.690
Percent Change From Baseline in Pruritus NRS Week 252	-51.01 Percent Change Standard Deviation 47.328
Percent Change From Baseline in Pruritus NRS Week 272	-46.23 Percent Change Standard Deviation 46.404

SECONDARY outcome

Timeframe: Up to 272 weeks (End of Study), "Baseline, Weeks 1, 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 252, 272 (End of Study)"

Outcome measures

Outcome measures
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline Week 1	11.9 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline Week 4	28.3 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline Week 16	39.3 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline Week 36	43.8 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline Week 52	45.9 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline Week 100	51.1 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline Week 124	48.8 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline Week 156	46.5 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline Week 172	54.1 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline Week 188	52.5 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline Week 204	56.9 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline Week 220	51.5 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline Week 236	51.3 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline Week 252	56.2 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline Week 272	50.0 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 272 weeks (End of Study), "Baseline, Weeks 1, 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 252, 272 (End of Study)"

Outcome measures

Outcome measures
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline Week 1	7.0 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline Week 4	18.6 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline Week 16	29.3 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline Week 36	33.3 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline Week 52	35.4 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline Week 100	41.4 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline Week 124	39.4 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline Week 156	35.6 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline Week 172	42.9 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline Week 188	40.9 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline Week 204	44.1 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline Week 220	40.2 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline Week 236	37.2 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline Week 252	42.7 Percentage of Participants
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline Week 272	36.0 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 272 weeks

Population: This included all participants who received any study drug.

Outcome measures

Outcome measures
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Percentage of Participants Requiring Rescue Treatment: Overall	1.7 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 272 weeks

Population: This included all participants who received any study drug.

Outcome measures

Outcome measures
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Percentage of Participants Requiring Rescue Treatment: Systemic Treatment	1.6 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 272 weeks

Population: This included all participants who received any study drug.

Outcome measures

Outcome measures
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Percentage of Participants Requiring Rescue Treatment: Phototherapy	0.0747 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 272 weeks (End of Study), "Baseline, Weeks 12, 24, 36, 48, 76, 100, 124, 148, 272 (End of Study)"

Population: Administered only to the subset of participants who fluently spoke the language for which a validated translation of the questionnaire was available, at time points according to the Schedule of Events as described in the study protocol. This included all participants who received any study drug.

The DLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on quality of life (QOL). The format is a simple response to 10 items, which assess QOL over the past week, with an overall scoring system of 0 to 30; a high score is indicative of a poor QOL

Outcome measures

Outcome measures
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI) Baseline of Current Study	8.5 Score on a scale Standard Deviation 7.11
Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI) Week 12	-4.9 Score on a scale Standard Deviation 5.93
Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI) Week 24	-6.0 Score on a scale Standard Deviation 6.41
Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI) Week 36	-6.5 Score on a scale Standard Deviation 6.51
Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI) Week 48	-5.6 Score on a scale Standard Deviation 6.20
Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI) Week 76	-7.2 Score on a scale Standard Deviation 6.41
Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI) Week 100	-7.3 Score on a scale Standard Deviation 6.66
Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI) Week 124	-7.9 Score on a scale Standard Deviation 6.40
Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI) Week 148	-8.3 Score on a scale Standard Deviation 5.14
Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI) End of Study	-3.6 Score on a scale Standard Deviation 7.37

SECONDARY outcome

Timeframe: Up to 272 weeks (End of Study), "Baseline, Weeks 12, 24, 36, 48, 76, 100, 124, 148, 272 (End of Study)"

Population: Administered only to the subset of participants who fluently speak the language for which a validated translation of the questionnaire is available. This included all participants who received any study drug.

The POEM is a 7-item, validated questionnaire used in clinical practice and clinical trials to assess disease symptoms in children and adults. The format is a response to 7 items (dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping) with a scoring system of 0 to 28; a high score is indicative of a poor QOL.

Outcome measures

Outcome measures
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Patient Oriented Eczema Measure (POEM) Week 12	-7.7 Score on a scale Standard Deviation 7.32
Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Patient Oriented Eczema Measure (POEM) Week 24	-9.3 Score on a scale Standard Deviation 7.44
Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Patient Oriented Eczema Measure (POEM) Week 36	-10.0 Score on a scale Standard Deviation 7.46
Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Patient Oriented Eczema Measure (POEM) Week 48	-8.8 Score on a scale Standard Deviation 7.46
Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Patient Oriented Eczema Measure (POEM) Week 76	-11.6 Score on a scale Standard Deviation 7.79
Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Patient Oriented Eczema Measure (POEM) Week 100	-11.4 Score on a scale Standard Deviation 7.30
Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Patient Oriented Eczema Measure (POEM) Week 124	-12.7 Score on a scale Standard Deviation 7.11
Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Patient Oriented Eczema Measure (POEM) Week 148	-10.5 Score on a scale Standard Deviation 6.06
Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Patient Oriented Eczema Measure (POEM) End of Study	-4.5 Score on a scale Standard Deviation 10.91

SECONDARY outcome

Timeframe: Up to 272 weeks (End of Study), "Baseline, Weeks 12, 24, 36, 48, 76, 100, 124, 148, 272 (End of Study)"

The EuroQOL 5-Dimension Health Questionnaire (EQ-5D) is a standardized measure of health status developed by the EuroQOL Group in order to provide a simple, generic measure of health for clinical and economic appraisal. The minimum value for the single index utility score is -0.594 (Best imaginable health state) and the maximum value for the single index utility score is 1 (Worst imaginable health state).

Outcome measures

Outcome measures
Measure	Dupilumab n=2677 Participants Participants received repeated doses of dupilumab
Changes From Parent Study Baseline to Prespecified Time Points Through the End of the Study: EuroQol-5D (EQ-5D) End of Study	0.1864 Score on a scale Standard Deviation 0.32838
Changes From Parent Study Baseline to Prespecified Time Points Through the End of the Study: EuroQol-5D (EQ-5D) Week 12	0.2769 Score on a scale Standard Deviation 0.31571
Changes From Parent Study Baseline to Prespecified Time Points Through the End of the Study: EuroQol-5D (EQ-5D) Week 24	0.3001 Score on a scale Standard Deviation 0.32062
Changes From Parent Study Baseline to Prespecified Time Points Through the End of the Study: EuroQol-5D (EQ-5D) Week 36	0.3056 Score on a scale Standard Deviation 0.33204
Changes From Parent Study Baseline to Prespecified Time Points Through the End of the Study: EuroQol-5D (EQ-5D) Week 48	0.2854 Score on a scale Standard Deviation 0.31017
Changes From Parent Study Baseline to Prespecified Time Points Through the End of the Study: EuroQol-5D (EQ-5D) Week 76	0.2965 Score on a scale Standard Deviation 0.30658
Changes From Parent Study Baseline to Prespecified Time Points Through the End of the Study: EuroQol-5D (EQ-5D) Week 100	0.3217 Score on a scale Standard Deviation 0.33832
Changes From Parent Study Baseline to Prespecified Time Points Through the End of the Study: EuroQol-5D (EQ-5D) Week 124	0.3242 Score on a scale Standard Deviation 0.28937
Changes From Parent Study Baseline to Prespecified Time Points Through the End of the Study: EuroQol-5D (EQ-5D) Week 148	0.3046 Score on a scale Standard Deviation 0.26337

SECONDARY outcome

Timeframe: Up to week 12

Population: The sub-study ADA population includes all treated patients who receive new dupilumab drug product and have at least one non-missing anti-dupilumab antibody result at any time during the sub-study period after the first dose of new dupilumab drug product.

Outcome measures

Outcome measures
Measure	Dupilumab n=50 Participants Participants received repeated doses of dupilumab
OPTIONAL SUB-STUDY: Ctrough of Functional Dupilumab in Serum Before and After Switching to the New Dupilumab Drug Product Week 0	65.9 mg/L Standard Deviation 40.8
OPTIONAL SUB-STUDY: Ctrough of Functional Dupilumab in Serum Before and After Switching to the New Dupilumab Drug Product Week 12	65.4 mg/L Standard Deviation 34.7

SECONDARY outcome

Timeframe: Up to 24 Weeks

For participants receiving dupilumab from a new manufacturing process, ADA baseline was defined as the baseline visit in the sub-study, or at the end of the main study, dependent on available data.

Outcome measures

Outcome data not reported

Adverse Events

Dupilumab

Serious events: 283 serious events

Other events: 1613 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Dupilumab n=2677 participants at risk Participants received repeated doses of dupilumab
Infections and infestations Appendicitis	0.22% 6/2677 • Number of events 6 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Corona virus infection	0.11% 3/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Erysipelas	0.11% 3/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Gastroenteritis	0.11% 3/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Pilonidal cyst	0.11% 3/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Chronic tonsillitis	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Diverticulitis	0.07% 2/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Eczema herpeticum	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Influenza	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Peritonsillar abscess	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Pneumonia	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Urosepsis	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Abdominal abscess	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Bronchitis	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Bronchopneumonia	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Cellulitis	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Chronic sinusitis	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Gastroenteritis bacterial	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Hand-foot-and-mouth disease	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Hepatitis A	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Herpes ophthalmic	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Herpes zoster disseminated	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Impetigo	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Infected dermal cyst	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Keratitis bacterial	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Lung infection	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Parotitis	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Periorbital cellulitis	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Perirectal abscess	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Pyelonephritis	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Superinfection bacterial	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Urinary tract infection	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Viral corneal ulcer	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Wound infection staphylococcal	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.30% 8/2677 • Number of events 14 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mycosis fungoides	0.11% 3/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.11% 3/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.11% 3/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.11% 3/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hodgkin's disease	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal proliferative breast lesion	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer female	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer stage I	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon adenoma	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Granular cell tumour	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hodgkin's disease lymphocyte predominance type stage III	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal cancer stage II	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian germ cell teratoma benign	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma metastatic	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasmacytoma	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer metastatic	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seminoma	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the tongue	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) T-cell lymphoma	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Ligament rupture	0.19% 5/2677 • Number of events 5 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Ankle fracture	0.15% 4/2677 • Number of events 4 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Joint dislocation	0.11% 3/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Meniscus injury	0.11% 3/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Clavicle fracture	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Contusion	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Lower limb fracture	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Upper limb fracture	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Alcohol poisoning	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Comminuted fracture	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Concussion	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Craniocerebral injury	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Fall	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Injury	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Ligament injury	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Ligament sprain	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Limb traumatic amputation	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Muscle injury	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Post procedural haemorrhage	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Pubis fracture	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Rib fracture	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Sternal fracture	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Thermal burn	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Transplant dysfunction	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Traumatic arthrosis	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Traumatic intracranial haemorrhage	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Injury, poisoning and procedural complications Wound dehiscence	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Musculoskeletal and connective tissue disorders Osteoarthritis	0.41% 11/2677 • Number of events 12 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.11% 3/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.11% 3/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Musculoskeletal and connective tissue disorders Arthralgia	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Musculoskeletal and connective tissue disorders Fibromyalgia	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Musculoskeletal and connective tissue disorders Foot deformity	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Nervous system disorders Syncope	0.19% 5/2677 • Number of events 6 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Nervous system disorders Migraine	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Nervous system disorders Amnesia	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Nervous system disorders Carotid artery stenosis	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Nervous system disorders Carpal tunnel syndrome	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Nervous system disorders Cerebrovascular accident	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Nervous system disorders Dizziness	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Nervous system disorders Epilepsy	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Nervous system disorders Generalised tonic-clonic seizure	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Nervous system disorders Hypoaesthesia	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Nervous system disorders Intracranial aneurysm	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Nervous system disorders Ischaemic cerebral infarction	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Nervous system disorders Migraine with aura	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Nervous system disorders Nerve compression	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Nervous system disorders Subarachnoid haemorrhage	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Nervous system disorders Thalamic infarction	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Gastrointestinal disorders Inguinal hernia	0.19% 5/2677 • Number of events 5 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Gastrointestinal disorders Colitis	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Gastrointestinal disorders Large intestine polyp	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Gastrointestinal disorders Umbilical hernia	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Gastrointestinal disorders Ascites	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Gastrointestinal disorders Diarrhoea	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Gastrointestinal disorders Diverticular perforation	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Gastrointestinal disorders Enterocolitis	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Gastrointestinal disorders Haematochezia	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Gastrointestinal disorders Hiatus hernia	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Gastrointestinal disorders Incarcerated umbilical hernia	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Gastrointestinal disorders Intestinal polyp	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Gastrointestinal disorders Pancreatitis chronic	0.04% 1/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Eye disorders Cataract	0.11% 3/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Eye disorders Ectropion	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Eye disorders Entropion	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Eye disorders Trichiasis	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Eye disorders Atopic keratoconjunctivitis	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Eye disorders Chalazion	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Eye disorders Corneal erosion	0.04% 1/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Eye disorders Corneal neovascularisation	0.04% 1/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Eye disorders Corneal perforation	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Eye disorders Eyelid cyst	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Eye disorders Keratoconus	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Eye disorders Mydriasis	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Eye disorders Optic neuropathy	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Eye disorders Retinal artery occlusion	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Eye disorders Retinal detachment	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Eye disorders Ulcerative keratitis	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Respiratory, thoracic and mediastinal disorders Nasal septum deviation	0.15% 4/2677 • Number of events 4 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Respiratory, thoracic and mediastinal disorders Asthma	0.11% 3/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Respiratory, thoracic and mediastinal disorders Choking	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Respiratory, thoracic and mediastinal disorders Nasal septum disorder	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Respiratory, thoracic and mediastinal disorders Nasal turbinate hypertrophy	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Respiratory, thoracic and mediastinal disorders Pneumothorax spontaneous	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Respiratory, thoracic and mediastinal disorders Status asthmaticus	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Skin and subcutaneous tissue disorders Dermatitis atopic	0.22% 6/2677 • Number of events 7 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Skin and subcutaneous tissue disorders Erythema nodosum	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Skin and subcutaneous tissue disorders Actinic keratosis	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Skin and subcutaneous tissue disorders Alopecia areata	0.04% 1/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Skin and subcutaneous tissue disorders Angioedema	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Skin and subcutaneous tissue disorders Drug eruption	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Skin and subcutaneous tissue disorders Eczema	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Skin and subcutaneous tissue disorders Pruritus generalised	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Skin and subcutaneous tissue disorders Skin ulcer	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Cardiac disorders Myocardial infarction	0.11% 3/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Cardiac disorders Atrial fibrillation	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Cardiac disorders Acute myocardial infarction	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Cardiac disorders Angina pectoris	0.04% 1/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Cardiac disorders Aortic valve incompetence	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Cardiac disorders Arrhythmia	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Cardiac disorders Atrial flutter	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Cardiac disorders Bundle branch block left	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Cardiac disorders Chordae tendinae rupture	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Cardiac disorders Coronary artery disease	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Cardiac disorders Myocardial ischaemia	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Cardiac disorders Prinzmetal angina	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Psychiatric disorders Depression	0.15% 4/2677 • Number of events 4 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Psychiatric disorders Panic attack	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Psychiatric disorders Alcohol abuse	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Psychiatric disorders Drug abuse	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Psychiatric disorders Emotional distress	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Psychiatric disorders Major depression	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Psychiatric disorders Psychotic disorder	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Psychiatric disorders "Schizophrenia, paranoid type"	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Psychiatric disorders Suicide attempt	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Hepatobiliary disorders Cholelithiasis	0.15% 4/2677 • Number of events 4 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Hepatobiliary disorders Acute hepatic failure	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Hepatobiliary disorders Bile duct stone	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Hepatobiliary disorders Cholecystitis	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Hepatobiliary disorders Cholestasis of pregnancy	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Hepatobiliary disorders Drug-induced liver injury	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Hepatobiliary disorders Hepatic cirrhosis	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Hepatobiliary disorders Hepatorenal syndrome	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Hepatobiliary disorders Jaundice cholestatic	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Renal and urinary disorders Nephrolithiasis	0.11% 3/2677 • Number of events 5 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Renal and urinary disorders Calculus ureteric	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Renal and urinary disorders Acute kidney injury	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Renal and urinary disorders Calculus urethral	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Renal and urinary disorders Haematuria	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Renal and urinary disorders IgA nephropathy	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Renal and urinary disorders Urethral stenosis	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Vascular disorders Deep vein thrombosis	0.11% 3/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Vascular disorders Aortic aneurysm	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Vascular disorders Aortic arteriosclerosis	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Vascular disorders Arteriosclerosis	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Vascular disorders Hypertension	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Vascular disorders Lymphoedema	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Vascular disorders Peripheral arterial occlusive disease	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Vascular disorders Varicose vein	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
General disorders Death	0.11% 3/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
General disorders Non-cardiac chest pain	0.07% 2/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
General disorders Chest pain	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
General disorders Cyst	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
General disorders Device dislocation	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Immune system disorders Anaphylactic reaction	0.11% 3/2677 • Number of events 4 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Immune system disorders Food allergy	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Immune system disorders Contrast media allergy	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Immune system disorders Sarcoidosis	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Immune system disorders Serum sickness	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Reproductive system and breast disorders Endometriosis	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Reproductive system and breast disorders Cervical dysplasia	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Reproductive system and breast disorders Menometrorrhagia	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Reproductive system and breast disorders Ovarian cyst	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Reproductive system and breast disorders Pelvic pain	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Reproductive system and breast disorders Uterine polyp	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.11% 3/2677 • Number of events 3 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Pregnancy, puerperium and perinatal conditions Abortion threatened	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Pregnancy, puerperium and perinatal conditions Haemorrhage in pregnancy	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Pregnancy, puerperium and perinatal conditions Premature separation of placenta	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Blood and lymphatic system disorders Febrile neutropenia	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Blood and lymphatic system disorders Haemolytic anaemia	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Blood and lymphatic system disorders Thrombocytopenia	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Congenital, familial and genetic disorders Atrial septal defect	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Congenital, familial and genetic disorders Congenital knee deformity	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Congenital, familial and genetic disorders Dolichocolon	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Endocrine disorders Goitre	0.07% 2/2677 • Number of events 2 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Endocrine disorders Thyroid mass	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Ear and labyrinth disorders Meniere's disease	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Investigations Intraocular pressure increased	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Metabolism and nutrition disorders Hypokalaemia	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Surgical and medical procedures Female sterilisation	0.04% 1/2677 • Number of events 1 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab

Other adverse events

Other adverse events
Measure	Dupilumab n=2677 participants at risk Participants received repeated doses of dupilumab
Infections and infestations Nasopharyngitis	28.9% 774/2677 • Number of events 1602 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Upper respiratory tract infection	13.6% 365/2677 • Number of events 567 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Conjunctivitis	10.3% 277/2677 • Number of events 417 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Infections and infestations Oral herpes	7.5% 200/2677 • Number of events 463 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Skin and subcutaneous tissue disorders Dermatitis atopic	16.7% 446/2677 • Number of events 787 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Eye disorders Conjunctivitis allergic	9.0% 242/2677 • Number of events 329 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
Nervous system disorders Headache	8.1% 218/2677 • Number of events 411 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab
General disorders Injection site reaction	5.2% 138/2677 • Number of events 506 • From first dose to end of study (plus extension), approximately 272 weeks Participants received repeated doses of dupilumab

Additional Information

Clinical Trials Administrator

Regeneron Pharmaceuticals, Inc.

Phone: 1-844-734-6643

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER