Atopic Dermatitis
Conditions
Keywords
Eczema
Brief summary
To assess the efficacy of multiple dupilumab dose-regimens, compared to placebo, in adult participants with moderate-to-severe atopic dermatitis (AD).
Interventions
DRUGDupilumab
DRUGPlacebo
Sponsors
Sanofi
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The inclusion criteria included, but were not limited to, the following: 1. Chronic Atopic Dermatitis that had been present for at least 3 years 2. History of inadequate response to out-patient treatment with topical medications, or for whom topical treatments were otherwise inadvisable (e.g, because of important side effects or safety risks) 3. Willing and able to comply with all clinic visits and study-related procedures The
Exclusion criteria
included, but were not limited to, the following: 1. Prior treatment with dupilumab (REGN668/SAR231893) 2. Presence of certain laboratory abnormalities at the screening visit 3. Treatment with an investigational drug within 8 weeks of baseline visit 4. Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit 5. Certain other treatments and medical procedures undertaken within a particular time frame prior to the baseline visit 6. Known history of human immunodeficiency virus (HIV) infection 7. History of malignancy within 5 years before the baseline visit (with certain exceptions) 8. Planned surgical procedure during the length of the study 9. High risk of parasite infection 10. Any other medical or psychological condition that in the opinion of the investigator or the sponsor's medical monitor, would place the participants at risk, interfere with participation in the study or interfere with interpretation of study results 11. Pregnant or breast-feeding women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Eczema Area and Severity Index Score (EASI) From Baseline to Week 16 | Baseline to Week 16 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved IGA Score Reduction of ≥2 at Week 16 | Week 16 | IGA is an assessment scale used to determine severity of 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. Therapeutic success is an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA score reduction from baseline of ≥2 points at Week 16 were reported. Values after first rescue medication were set to missing and participants with missing IGA score at Week 16 were treated as a non-responders. |
| Percent Change in Peak Weekly Averaged Pruritus Numerical Rating Scores (NRS) From Baseline to Week 16 | Baseline to Week 16 | Pruritus NRS is an assessment tool that is used to report the intensity of participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). |
| Absolute Change in Peak Weekly Averaged Pruritus NRS From Baseline to Week 16 | Baseline to Week 16 | Pruritus NRS is an assessment tool that is used to report the intensity of participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). |
| Absolute Change in EASI Score From Baseline to Week 16 | Baseline to Week 16 | 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. |
| Percent Change in SCORing Atopic Dermatitis (SCORAD) Scores From Baseline to Week 16 | Baseline to Week 16 | SCORAD is a clinical tool for assessing the severity of AD developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23-31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). |
| Absolute Change in SCORAD Scores From Baseline to Week 16 | Baseline to Week 16 | SCORAD is a clinical tool for assessing the severity of AD developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23-31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). |
| Percentage of Participants Who Achieved Investigator's Global Assessment (IGA) Response at Week 16 | Week 16 | IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a static 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Values after first rescue medication were set to missing and participants with missing IGA score at Week 16 were treated as a non-responders. |
| Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Week 16 | SCORAD is a clinical tool for assessing the severity of AD developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23-31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). SCORAD-50, SCORAD-75 and SCORAD-90 responders were the participants who achieved ≥50%, ≥75% and ≥90% overall improvement in SCORAD score respectively from baseline to Week 16. |
| Percent Change in Patient Oriented Eczema Measure (POEM) Scores From Baseline to Week 16 | Baseline to Week 16 | POEM is a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life \[QOL\]). |
| Absolute Change in POEM Scores From Baseline to Week 16 | Baseline to Week 16 | POEM is a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life \[QOL\]). |
| Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Baseline to Week 16 | Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0=none, 1=mild, 2=moderate and 3=severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease). |
| Changes in GISS Cumulative Score From Baseline to Week 16 | Baseline to Week 16 | Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none,1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease). |
| Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score (EASI-50, EASI-75 and EASI-90 Respectively) at Week 16 | Week 16 | 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. EASI-50, EASI-75 and EASI-90 responders were the participants who achieved ≥50%, ≥75% and ≥90% overall improvement in EASI score respectively from baseline to Week 16. |
Countries
Canada, Czechia, Germany, Hungary, Japan, Poland, United States
Participant flow
Recruitment details
The study was conducted at 95 study sites in 7 countries. A total of 452 participants were screened between 15 May 2013 and 10 January 2014. 380 participants were randomized and 379 were treated. 72 participants were screen failures mainly due to exclusion criteria met and inclusion criteria not met.
Pre-assignment details
Randomization was stratified by disease severity (moderate Investigator's global assessment \[IGA\] = 3 versus severe IGA = 4 atopic dermatitis) and region (Japan versus rest of world). Assignment to arms was done centrally in 1:1:1:1:1:1 ratio for Dupilumab (300 mg qw; 300 mg q2w; 200 mg q2w; 300 mg q4w and 100 mg q4w) and Placebo.
Participants by arm
| Arm | Count |
|---|---|
| Dupilumab 300 mg qw Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection qw from Week 1 to Week 15. | 63 |
| Dupilumab 300 mg q2w Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single injection of Placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 15. | 64 |
| Dupilumab 200 mg q2w Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single injection of Placebo (for Dupilumab) alternating with single 200 mg injection of Dupilumab q2w from Week 1 to Week 15. | 61 |
| Dupilumab 300 mg q4w Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab q4w and Placebo (for Dupilumab) qw (when Dupilumab not administered) from Week 1 to Week 15. | 65 |
| Dupilumab 100 mg q4w Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single 100 mg injection of Dupilumab q4w and Placebo (for Dupilumab) qw (when Dupilumab not administered) from Week 1 to Week 15. | 65 |
| Placebo Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15. | 61 |
| Total | 379 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 3 | 1 | 2 | 2 |
| Overall Study | Lack of Efficacy | 1 | 1 | 5 | 0 | 7 | 9 |
| Overall Study | Lost to Follow-up | 1 | 2 | 3 | 0 | 3 | 2 |
| Overall Study | Other than specified above | 0 | 2 | 11 | 3 | 5 | 3 |
| Overall Study | Physician Decision | 1 | 3 | 1 | 3 | 4 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 3 | 4 | 3 | 2 | 2 |
Baseline characteristics
| Characteristic | Dupilumab 300 mg qw | Dupilumab 300 mg q2w | Dupilumab 200 mg q2w | Dupilumab 300 mg q4w | Dupilumab 100 mg q4w | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 36.2 years STANDARD_DEVIATION 10.74 | 39.4 years STANDARD_DEVIATION 12.06 | 35.8 years STANDARD_DEVIATION 14.9 | 36.8 years STANDARD_DEVIATION 10.77 | 36.6 years STANDARD_DEVIATION 11.55 | 37.2 years STANDARD_DEVIATION 13.1 | 37.0 years STANDARD_DEVIATION 12.06 |
| Sex: Female, Male Female | 20 Participants | 23 Participants | 25 Participants | 25 Participants | 31 Participants | 21 Participants | 145 Participants |
| Sex: Female, Male Male | 43 Participants | 41 Participants | 36 Participants | 40 Participants | 34 Participants | 40 Participants | 234 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 35 / 63 | 34 / 64 | 34 / 61 | 39 / 65 | 38 / 65 | 38 / 61 |
| serious Total, serious adverse events | 1 / 63 | 2 / 64 | 1 / 61 | 3 / 65 | 5 / 65 | 4 / 61 |
Outcome results
Primary
Percent Change in Eczema Area and Severity Index Score (EASI) From Baseline to Week 16
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.
Time frame: Baseline to Week 16
Population: Full analysis set (FAS) that included all randomized participants who received at least 1 dose of study drug. Here, number of participants analyzed = participants with EASI score assessment at specified time-point. Efficacy data was set to missing after use of rescue medication. Missing values imputed by last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dupilumab 300 mg qw | Percent Change in Eczema Area and Severity Index Score (EASI) From Baseline to Week 16 | -75.5 Percent change | Standard Deviation 26.86 |
| Dupilumab 300 mg q2w | Percent Change in Eczema Area and Severity Index Score (EASI) From Baseline to Week 16 | -70.5 Percent change | Standard Deviation 35.09 |
| Dupilumab 200 mg q2w | Percent Change in Eczema Area and Severity Index Score (EASI) From Baseline to Week 16 | -67.4 Percent change | Standard Deviation 31.97 |
| Dupilumab 300 mg q4w | Percent Change in Eczema Area and Severity Index Score (EASI) From Baseline to Week 16 | -64.9 Percent change | Standard Deviation 37.21 |
| Dupilumab 100 mg q4w | Percent Change in Eczema Area and Severity Index Score (EASI) From Baseline to Week 16 | -46.7 Percent change | Standard Deviation 41.96 |
| Placebo | Percent Change in Eczema Area and Severity Index Score (EASI) From Baseline to Week 16 | -20.2 Percent change | Standard Deviation 46.15 |
Comparison: LS mean and standard error were obtained using analysis of covariance (ANCOVA) model with treatment and randomization strata (moderate vs severe;Japan vs rest of world) and relevant baseline values as covariates. Multiplicity was controlled using hierarchical testing procedure:highest dose vs. placebo was tested first. Comparison order was 300 mg qw,300 mg q2w,200 mg q2w,300 mg q4w \& 100 mg q4w, vs placebo respectively. Testing continues only if previous comparison was statistically significant.p-value: <0.000195% CI: [-68.9, -42.4]ANCOVA
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-63.3, -37]ANCOVA
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-60.6, -34.1]ANCOVA
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-58.5, -32.3]ANCOVA
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-39.8, -13.7]ANCOVA
Secondary
Absolute Change in EASI Score From Baseline to Week 16
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.
Time frame: Baseline to Week 16
Population: Analysis was performed on FAS. Here, number of participants analyzed = participants with EASI score assessment at specified time-points. Efficacy data was set to missing after use of rescue medication. Missing values imputed by LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Dupilumab 300 mg qw | Absolute Change in EASI Score From Baseline to Week 16 | Week 16 | 7.2 Units on a scale | Standard Error 8.83 |
| Dupilumab 300 mg qw | Absolute Change in EASI Score From Baseline to Week 16 | Change at Week 16 | -23.1 Units on a scale | Standard Error 1.7 |
| Dupilumab 300 mg qw | Absolute Change in EASI Score From Baseline to Week 16 | Baseline | 30.1 Units on a scale | Standard Error 11.23 |
| Dupilumab 300 mg q2w | Absolute Change in EASI Score From Baseline to Week 16 | Week 16 | 10.7 Units on a scale | Standard Error 12.89 |
| Dupilumab 300 mg q2w | Absolute Change in EASI Score From Baseline to Week 16 | Change at Week 16 | -21.1 Units on a scale | Standard Error 1.68 |
| Dupilumab 300 mg q2w | Absolute Change in EASI Score From Baseline to Week 16 | Baseline | 33.8 Units on a scale | Standard Error 14.52 |
| Dupilumab 200 mg q2w | Absolute Change in EASI Score From Baseline to Week 16 | Change at Week 16 | -20.7 Units on a scale | Standard Error 1.71 |
| Dupilumab 200 mg q2w | Absolute Change in EASI Score From Baseline to Week 16 | Baseline | 32.9 Units on a scale | Standard Error 15.5 |
| Dupilumab 200 mg q2w | Absolute Change in EASI Score From Baseline to Week 16 | Week 16 | 10.9 Units on a scale | Standard Error 12.41 |
| Dupilumab 300 mg q4w | Absolute Change in EASI Score From Baseline to Week 16 | Baseline | 29.4 Units on a scale | Standard Error 11.48 |
| Dupilumab 300 mg q4w | Absolute Change in EASI Score From Baseline to Week 16 | Week 16 | 9.8 Units on a scale | Standard Error 11.16 |
| Dupilumab 300 mg q4w | Absolute Change in EASI Score From Baseline to Week 16 | Change at Week 16 | -20.4 Units on a scale | Standard Error 1.62 |
| Dupilumab 100 mg q4w | Absolute Change in EASI Score From Baseline to Week 16 | Change at Week 16 | -13.8 Units on a scale | Standard Error 1.64 |
| Dupilumab 100 mg q4w | Absolute Change in EASI Score From Baseline to Week 16 | Baseline | 32.2 Units on a scale | Standard Error 13.49 |
| Dupilumab 100 mg q4w | Absolute Change in EASI Score From Baseline to Week 16 | Week 16 | 17.4 Units on a scale | Standard Error 15.28 |
| Placebo | Absolute Change in EASI Score From Baseline to Week 16 | Week 16 | 25.6 Units on a scale | Standard Error 18.32 |
| Placebo | Absolute Change in EASI Score From Baseline to Week 16 | Baseline | 32.9 Units on a scale | Standard Error 13.77 |
| Placebo | Absolute Change in EASI Score From Baseline to Week 16 | Change at Week 16 | -5.8 Units on a scale | Standard Error 1.71 |
Secondary
Absolute Change in Peak Weekly Averaged Pruritus NRS From Baseline to Week 16
Pruritus NRS is an assessment tool that is used to report the intensity of participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]).
Time frame: Baseline to Week 16
Population: Analysis was performed on FAS. Here, number of participants analyzed =participants with pruritus NRS assessment at specified time-points. Efficacy data was set to missing after use of rescue medication. Missing values imputed by LOCF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dupilumab 300 mg qw | Absolute Change in Peak Weekly Averaged Pruritus NRS From Baseline to Week 16 | Week 16 | 3.07 units on a scale | Standard Deviation 2.148 |
| Dupilumab 300 mg qw | Absolute Change in Peak Weekly Averaged Pruritus NRS From Baseline to Week 16 | Change at Week 16 | -3.48 units on a scale | Standard Deviation 2.32 |
| Dupilumab 300 mg qw | Absolute Change in Peak Weekly Averaged Pruritus NRS From Baseline to Week 16 | Baseline | 6.54 units on a scale | Standard Deviation 1.54 |
| Dupilumab 300 mg q2w | Absolute Change in Peak Weekly Averaged Pruritus NRS From Baseline to Week 16 | Week 16 | 3.64 units on a scale | Standard Deviation 2.388 |
| Dupilumab 300 mg q2w | Absolute Change in Peak Weekly Averaged Pruritus NRS From Baseline to Week 16 | Baseline | 6.74 units on a scale | Standard Deviation 2.072 |
| Dupilumab 300 mg q2w | Absolute Change in Peak Weekly Averaged Pruritus NRS From Baseline to Week 16 | Change at Week 16 | -3.16 units on a scale | Standard Deviation 2.467 |
| Dupilumab 200 mg q2w | Absolute Change in Peak Weekly Averaged Pruritus NRS From Baseline to Week 16 | Week 16 | 4.21 units on a scale | Standard Deviation 2.763 |
| Dupilumab 200 mg q2w | Absolute Change in Peak Weekly Averaged Pruritus NRS From Baseline to Week 16 | Baseline | 6.98 units on a scale | Standard Deviation 2.315 |
| Dupilumab 200 mg q2w | Absolute Change in Peak Weekly Averaged Pruritus NRS From Baseline to Week 16 | Change at Week 16 | -2.77 units on a scale | Standard Deviation 2.595 |
| Dupilumab 300 mg q4w | Absolute Change in Peak Weekly Averaged Pruritus NRS From Baseline to Week 16 | Change at Week 16 | -2.79 units on a scale | Standard Deviation 2.609 |
| Dupilumab 300 mg q4w | Absolute Change in Peak Weekly Averaged Pruritus NRS From Baseline to Week 16 | Baseline | 6.84 units on a scale | Standard Deviation 1.853 |
| Dupilumab 300 mg q4w | Absolute Change in Peak Weekly Averaged Pruritus NRS From Baseline to Week 16 | Week 16 | 3.99 units on a scale | Standard Deviation 2.449 |
| Dupilumab 100 mg q4w | Absolute Change in Peak Weekly Averaged Pruritus NRS From Baseline to Week 16 | Week 16 | 5.26 units on a scale | Standard Deviation 2.465 |
| Dupilumab 100 mg q4w | Absolute Change in Peak Weekly Averaged Pruritus NRS From Baseline to Week 16 | Baseline | 6.71 units on a scale | Standard Deviation 1.882 |
| Dupilumab 100 mg q4w | Absolute Change in Peak Weekly Averaged Pruritus NRS From Baseline to Week 16 | Change at Week 16 | -1.46 units on a scale | Standard Deviation 2.038 |
| Placebo | Absolute Change in Peak Weekly Averaged Pruritus NRS From Baseline to Week 16 | Week 16 | 6.05 units on a scale | Standard Deviation 2.312 |
| Placebo | Absolute Change in Peak Weekly Averaged Pruritus NRS From Baseline to Week 16 | Baseline | 6.34 units on a scale | Standard Deviation 1.832 |
| Placebo | Absolute Change in Peak Weekly Averaged Pruritus NRS From Baseline to Week 16 | Change at Week 16 | -0.27 units on a scale | Standard Deviation 2.28 |
Secondary
Absolute Change in POEM Scores From Baseline to Week 16
POEM is a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life \[QOL\]).
Time frame: Baseline to Week 16
Population: Analysis was performed on FAS. Here, number of participants analyzed = participants with POEM score assessment at specified time-points. Missing values imputed by LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dupilumab 300 mg qw | Absolute Change in POEM Scores From Baseline to Week 16 | -12.1 units on a scale | Standard Error 0.88 |
| Dupilumab 300 mg q2w | Absolute Change in POEM Scores From Baseline to Week 16 | -9.8 units on a scale | Standard Error 0.87 |
| Dupilumab 200 mg q2w | Absolute Change in POEM Scores From Baseline to Week 16 | -10.4 units on a scale | Standard Error 0.89 |
| Dupilumab 300 mg q4w | Absolute Change in POEM Scores From Baseline to Week 16 | -9.9 units on a scale | Standard Error 0.85 |
| Dupilumab 100 mg q4w | Absolute Change in POEM Scores From Baseline to Week 16 | -3.3 units on a scale | Standard Error 0.85 |
| Placebo | Absolute Change in POEM Scores From Baseline to Week 16 | -1.1 units on a scale | Standard Error 0.9 |
Secondary
Absolute Change in SCORAD Scores From Baseline to Week 16
SCORAD is a clinical tool for assessing the severity of AD developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23-31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease).
Time frame: Baseline to Week 16
Population: Analysis was performed on FAS. Here, number of participants analyzed = participants with SCORAD score assessment at specified time-points. Missing values imputed by LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dupilumab 300 mg qw | Absolute Change in SCORAD Scores From Baseline to Week 16 | -38.2 units on a scale | Standard Error 2.76 |
| Dupilumab 300 mg q2w | Absolute Change in SCORAD Scores From Baseline to Week 16 | -34.4 units on a scale | Standard Error 2.71 |
| Dupilumab 200 mg q2w | Absolute Change in SCORAD Scores From Baseline to Week 16 | -30.9 units on a scale | Standard Error 2.76 |
| Dupilumab 300 mg q4w | Absolute Change in SCORAD Scores From Baseline to Week 16 | -33.1 units on a scale | Standard Error 2.64 |
| Dupilumab 100 mg q4w | Absolute Change in SCORAD Scores From Baseline to Week 16 | -18.0 units on a scale | Standard Error 2.66 |
| Placebo | Absolute Change in SCORAD Scores From Baseline to Week 16 | -10.5 units on a scale | Standard Error 2.77 |
Secondary
Changes in GISS Cumulative Score From Baseline to Week 16
Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none,1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease).
Time frame: Baseline to Week 16
Population: Analysis was performed on FAS. Here, number of participants analyzed = participants with GISS score assessment at specified time-points. Missing values imputed by LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dupilumab 300 mg qw | Changes in GISS Cumulative Score From Baseline to Week 16 | -4.6 units on a scale | Standard Error 0.38 |
| Dupilumab 300 mg q2w | Changes in GISS Cumulative Score From Baseline to Week 16 | -4.5 units on a scale | Standard Error 0.37 |
| Dupilumab 200 mg q2w | Changes in GISS Cumulative Score From Baseline to Week 16 | -3.9 units on a scale | Standard Error 0.38 |
| Dupilumab 300 mg q4w | Changes in GISS Cumulative Score From Baseline to Week 16 | -4.3 units on a scale | Standard Error 0.37 |
| Dupilumab 100 mg q4w | Changes in GISS Cumulative Score From Baseline to Week 16 | -2.3 units on a scale | Standard Error 0.37 |
| Placebo | Changes in GISS Cumulative Score From Baseline to Week 16 | -1.2 units on a scale | Standard Error 0.38 |
Secondary
Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16
Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0=none, 1=mild, 2=moderate and 3=severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease).
Time frame: Baseline to Week 16
Population: Analysis was performed on FAS. Here, number of participants analyzed = participants with GISS score assessment at specified time-points. Missing values imputed by LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Dupilumab 300 mg qw | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Erythema | -0.9 units on a scale | Standard Error 0.1 |
| Dupilumab 300 mg qw | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Infiltration/Papulation | -1.2 units on a scale | Standard Error 0.11 |
| Dupilumab 300 mg qw | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Excoriations | -1.4 units on a scale | Standard Error 0.11 |
| Dupilumab 300 mg qw | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Lichenification | -1.1 units on a scale | Standard Error 0.12 |
| Dupilumab 300 mg q2w | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Excoriations | -1.4 units on a scale | Standard Error 0.11 |
| Dupilumab 300 mg q2w | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Infiltration/Papulation | -1.1 units on a scale | Standard Error 0.11 |
| Dupilumab 300 mg q2w | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Erythema | -0.9 units on a scale | Standard Error 0.1 |
| Dupilumab 300 mg q2w | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Lichenification | -1.1 units on a scale | Standard Error 0.11 |
| Dupilumab 200 mg q2w | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Lichenification | -1.0 units on a scale | Standard Error 0.12 |
| Dupilumab 200 mg q2w | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Excoriations | -1.1 units on a scale | Standard Error 0.11 |
| Dupilumab 200 mg q2w | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Infiltration/Papulation | -1.0 units on a scale | Standard Error 0.11 |
| Dupilumab 200 mg q2w | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Erythema | -0.8 units on a scale | Standard Error 0.1 |
| Dupilumab 300 mg q4w | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Erythema | -0.8 units on a scale | Standard Error 0.1 |
| Dupilumab 300 mg q4w | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Lichenification | -1.1 units on a scale | Standard Error 0.11 |
| Dupilumab 300 mg q4w | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Infiltration/Papulation | -1.1 units on a scale | Standard Error 0.1 |
| Dupilumab 300 mg q4w | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Excoriations | -1.3 units on a scale | Standard Error 0.11 |
| Dupilumab 100 mg q4w | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Excoriations | -0.6 units on a scale | Standard Error 0.11 |
| Dupilumab 100 mg q4w | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Lichenification | -0.7 units on a scale | Standard Error 0.11 |
| Dupilumab 100 mg q4w | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Infiltration/Papulation | -0.6 units on a scale | Standard Error 0.11 |
| Dupilumab 100 mg q4w | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Erythema | -0.4 units on a scale | Standard Error 0.1 |
| Placebo | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Infiltration/Papulation | -0.3 units on a scale | Standard Error 0.11 |
| Placebo | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Excoriations | -0.4 units on a scale | Standard Error 0.11 |
| Placebo | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Lichenification | -0.3 units on a scale | Standard Error 0.12 |
| Placebo | Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From Baseline to Week 16 | Erythema | -0.2 units on a scale | Standard Error 0.1 |
Secondary
Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score (EASI-50, EASI-75 and EASI-90 Respectively) at Week 16
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. EASI-50, EASI-75 and EASI-90 responders were the participants who achieved ≥50%, ≥75% and ≥90% overall improvement in EASI score respectively from baseline to Week 16.
Time frame: Week 16
Population: Analysis was performed on FAS. Participants with a missing EASI score at Week 16 were treated as non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dupilumab 300 mg qw | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score (EASI-50, EASI-75 and EASI-90 Respectively) at Week 16 | Reduction of 75% | 60.3 Percentage of participants |
| Dupilumab 300 mg qw | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score (EASI-50, EASI-75 and EASI-90 Respectively) at Week 16 | Reduction of 90% | 36.5 Percentage of participants |
| Dupilumab 300 mg qw | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score (EASI-50, EASI-75 and EASI-90 Respectively) at Week 16 | Reduction of 50% | 82.5 Percentage of participants |
| Dupilumab 300 mg q2w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score (EASI-50, EASI-75 and EASI-90 Respectively) at Week 16 | Reduction of 75% | 53.1 Percentage of participants |
| Dupilumab 300 mg q2w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score (EASI-50, EASI-75 and EASI-90 Respectively) at Week 16 | Reduction of 90% | 29.7 Percentage of participants |
| Dupilumab 300 mg q2w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score (EASI-50, EASI-75 and EASI-90 Respectively) at Week 16 | Reduction of 50% | 78.1 Percentage of participants |
| Dupilumab 200 mg q2w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score (EASI-50, EASI-75 and EASI-90 Respectively) at Week 16 | Reduction of 90% | 31.1 Percentage of participants |
| Dupilumab 200 mg q2w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score (EASI-50, EASI-75 and EASI-90 Respectively) at Week 16 | Reduction of 50% | 62.3 Percentage of participants |
| Dupilumab 200 mg q2w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score (EASI-50, EASI-75 and EASI-90 Respectively) at Week 16 | Reduction of 75% | 55.7 Percentage of participants |
| Dupilumab 300 mg q4w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score (EASI-50, EASI-75 and EASI-90 Respectively) at Week 16 | Reduction of 50% | 70.8 Percentage of participants |
| Dupilumab 300 mg q4w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score (EASI-50, EASI-75 and EASI-90 Respectively) at Week 16 | Reduction of 75% | 49.2 Percentage of participants |
| Dupilumab 300 mg q4w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score (EASI-50, EASI-75 and EASI-90 Respectively) at Week 16 | Reduction of 90% | 29.2 Percentage of participants |
| Dupilumab 100 mg q4w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score (EASI-50, EASI-75 and EASI-90 Respectively) at Week 16 | Reduction of 90% | 15.4 Percentage of participants |
| Dupilumab 100 mg q4w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score (EASI-50, EASI-75 and EASI-90 Respectively) at Week 16 | Reduction of 50% | 44.6 Percentage of participants |
| Dupilumab 100 mg q4w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score (EASI-50, EASI-75 and EASI-90 Respectively) at Week 16 | Reduction of 75% | 29.2 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score (EASI-50, EASI-75 and EASI-90 Respectively) at Week 16 | Reduction of 75% | 11.5 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score (EASI-50, EASI-75 and EASI-90 Respectively) at Week 16 | Reduction of 50% | 29.5 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score (EASI-50, EASI-75 and EASI-90 Respectively) at Week 16 | Reduction of 90% | 3.3 Percentage of participants |
Secondary
Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16
SCORAD is a clinical tool for assessing the severity of AD developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23-31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). SCORAD-50, SCORAD-75 and SCORAD-90 responders were the participants who achieved ≥50%, ≥75% and ≥90% overall improvement in SCORAD score respectively from baseline to Week 16.
Time frame: Week 16
Population: Analysis was performed on FAS. Participants with a missing SCORAD score at Week 16 were treated as non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dupilumab 300 mg qw | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Reduction of 75% | 23.8 Percentage of participants |
| Dupilumab 300 mg qw | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Reduction of 90% | 6.3 Percentage of participants |
| Dupilumab 300 mg qw | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Reduction of 50% | 68.3 Percentage of participants |
| Dupilumab 300 mg q2w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Reduction of 75% | 25.0 Percentage of participants |
| Dupilumab 300 mg q2w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Reduction of 90% | 6.3 Percentage of participants |
| Dupilumab 300 mg q2w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Reduction of 50% | 59.4 Percentage of participants |
| Dupilumab 200 mg q2w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Reduction of 75% | 16.4 Percentage of participants |
| Dupilumab 200 mg q2w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Reduction of 50% | 52.5 Percentage of participants |
| Dupilumab 200 mg q2w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Reduction of 90% | 4.9 Percentage of participants |
| Dupilumab 300 mg q4w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Reduction of 90% | 3.1 Percentage of participants |
| Dupilumab 300 mg q4w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Reduction of 50% | 55.4 Percentage of participants |
| Dupilumab 300 mg q4w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Reduction of 75% | 21.5 Percentage of participants |
| Dupilumab 100 mg q4w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Reduction of 50% | 26.2 Percentage of participants |
| Dupilumab 100 mg q4w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Reduction of 75% | 7.7 Percentage of participants |
| Dupilumab 100 mg q4w | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Reduction of 90% | 3.1 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Reduction of 75% | 3.3 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Reduction of 50% | 19.7 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Reduction of 90% | 0.0 Percentage of participants |
Secondary
Percentage of Participants Who Achieved IGA Score Reduction of ≥2 at Week 16
IGA is an assessment scale used to determine severity of 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. Therapeutic success is an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA score reduction from baseline of ≥2 points at Week 16 were reported. Values after first rescue medication were set to missing and participants with missing IGA score at Week 16 were treated as a non-responders.
Time frame: Week 16
Population: Analysis was performed on FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab 300 mg qw | Percentage of Participants Who Achieved IGA Score Reduction of ≥2 at Week 16 | 50.8 Percentage of participants |
| Dupilumab 300 mg q2w | Percentage of Participants Who Achieved IGA Score Reduction of ≥2 at Week 16 | 46.9 Percentage of participants |
| Dupilumab 200 mg q2w | Percentage of Participants Who Achieved IGA Score Reduction of ≥2 at Week 16 | 42.6 Percentage of participants |
| Dupilumab 300 mg q4w | Percentage of Participants Who Achieved IGA Score Reduction of ≥2 at Week 16 | 35.4 Percentage of participants |
| Dupilumab 100 mg q4w | Percentage of Participants Who Achieved IGA Score Reduction of ≥2 at Week 16 | 20.0 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved IGA Score Reduction of ≥2 at Week 16 | 9.8 Percentage of participants |
Secondary
Percentage of Participants Who Achieved Investigator's Global Assessment (IGA) Response at Week 16
IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a static 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Values after first rescue medication were set to missing and participants with missing IGA score at Week 16 were treated as a non-responders.
Time frame: Week 16
Population: Analysis was performed on FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab 300 mg qw | Percentage of Participants Who Achieved Investigator's Global Assessment (IGA) Response at Week 16 | 33.3 Percentage of participants |
| Dupilumab 300 mg q2w | Percentage of Participants Who Achieved Investigator's Global Assessment (IGA) Response at Week 16 | 29.7 Percentage of participants |
| Dupilumab 200 mg q2w | Percentage of Participants Who Achieved Investigator's Global Assessment (IGA) Response at Week 16 | 27.9 Percentage of participants |
| Dupilumab 300 mg q4w | Percentage of Participants Who Achieved Investigator's Global Assessment (IGA) Response at Week 16 | 21.5 Percentage of participants |
| Dupilumab 100 mg q4w | Percentage of Participants Who Achieved Investigator's Global Assessment (IGA) Response at Week 16 | 12.3 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved Investigator's Global Assessment (IGA) Response at Week 16 | 1.6 Percentage of participants |
Secondary
Percent Change in Patient Oriented Eczema Measure (POEM) Scores From Baseline to Week 16
POEM is a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life \[QOL\]).
Time frame: Baseline to Week 16
Population: Analysis was performed on FAS. Here, number of participants analyzed = participants with POEM score assessment at specified time-points. Missing values imputed by LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dupilumab 300 mg qw | Percent Change in Patient Oriented Eczema Measure (POEM) Scores From Baseline to Week 16 | -57.3 Percent change | Standard Error 4.52 |
| Dupilumab 300 mg q2w | Percent Change in Patient Oriented Eczema Measure (POEM) Scores From Baseline to Week 16 | -44.0 Percent change | Standard Error 4.44 |
| Dupilumab 200 mg q2w | Percent Change in Patient Oriented Eczema Measure (POEM) Scores From Baseline to Week 16 | -49.2 Percent change | Standard Error 5.54 |
| Dupilumab 300 mg q4w | Percent Change in Patient Oriented Eczema Measure (POEM) Scores From Baseline to Week 16 | -46.6 Percent change | Standard Error 4.33 |
| Dupilumab 100 mg q4w | Percent Change in Patient Oriented Eczema Measure (POEM) Scores From Baseline to Week 16 | -14.2 Percent change | Standard Error 4.35 |
| Placebo | Percent Change in Patient Oriented Eczema Measure (POEM) Scores From Baseline to Week 16 | 0.2 Percent change | Standard Error 4.61 |
Secondary
Percent Change in Peak Weekly Averaged Pruritus Numerical Rating Scores (NRS) From Baseline to Week 16
Pruritus NRS is an assessment tool that is used to report the intensity of participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]).
Time frame: Baseline to Week 16
Population: Analysis was performed on FAS. Here, number of participants analyzed = participants with pruritus NRS assessment at specified time-point. Efficacy data was set to missing after use of rescue medication. Missing values imputed by LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dupilumab 300 mg qw | Percent Change in Peak Weekly Averaged Pruritus Numerical Rating Scores (NRS) From Baseline to Week 16 | -52.85 Percent change | Standard Deviation 31.368 |
| Dupilumab 300 mg q2w | Percent Change in Peak Weekly Averaged Pruritus Numerical Rating Scores (NRS) From Baseline to Week 16 | -46.22 Percent change | Standard Deviation 31.964 |
| Dupilumab 200 mg q2w | Percent Change in Peak Weekly Averaged Pruritus Numerical Rating Scores (NRS) From Baseline to Week 16 | -40.6 Percent change | Standard Deviation 33.073 |
| Dupilumab 300 mg q4w | Percent Change in Peak Weekly Averaged Pruritus Numerical Rating Scores (NRS) From Baseline to Week 16 | -38.69 Percent change | Standard Deviation 38.366 |
| Dupilumab 100 mg q4w | Percent Change in Peak Weekly Averaged Pruritus Numerical Rating Scores (NRS) From Baseline to Week 16 | -21.47 Percent change | Standard Deviation 32.952 |
| Placebo | Percent Change in Peak Weekly Averaged Pruritus Numerical Rating Scores (NRS) From Baseline to Week 16 | -0.43 Percent change | Standard Deviation 38.423 |
Secondary
Percent Change in SCORing Atopic Dermatitis (SCORAD) Scores From Baseline to Week 16
SCORAD is a clinical tool for assessing the severity of AD developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23-31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease).
Time frame: Baseline to Week 16
Population: Analysis was performed on FAS. Here, number of participants analyzed = participants with SCORAD score assessment at specified time-points. Missing values imputed by LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dupilumab 300 mg qw | Percent Change in SCORing Atopic Dermatitis (SCORAD) Scores From Baseline to Week 16 | -56.9 Percent change | Standard Error 4.12 |
| Dupilumab 300 mg q2w | Percent Change in SCORing Atopic Dermatitis (SCORAD) Scores From Baseline to Week 16 | -51.2 Percent change | Standard Error 4.05 |
| Dupilumab 200 mg q2w | Percent Change in SCORing Atopic Dermatitis (SCORAD) Scores From Baseline to Week 16 | -46.0 Percent change | Standard Error 4.12 |
| Dupilumab 300 mg q4w | Percent Change in SCORing Atopic Dermatitis (SCORAD) Scores From Baseline to Week 16 | -48.8 Percent change | Standard Error 3.95 |
| Dupilumab 100 mg q4w | Percent Change in SCORing Atopic Dermatitis (SCORAD) Scores From Baseline to Week 16 | -26.6 Percent change | Standard Error 3.98 |
| Placebo | Percent Change in SCORing Atopic Dermatitis (SCORAD) Scores From Baseline to Week 16 | -13.8 Percent change | Standard Error 4.14 |