Clinically Meaningful Responses to Dupilumab in Adolescents with Uncontrolled Moderate-to-Severe Atopic Dermatitis: Post-hoc Analyses from a Randomized Clinical Trial

Amy S. Paller, Ashish Bansal, Eric L. Simpson, Mark Boguniewicz, Andrew Blauvelt, Elaine C. Siegfried, Emma Guttman-Yassky, Thomas Hultsch, Zhen Chen, Paola Mina-Osorio, Yufang Lu, Ana B. Rossi, Xinyi He, Mohamed Kamal, Neil M.H. Graham, Gianluca Pirozzi, Marcella Ruddy, Laurent Eckert, Abhijit Gadkari

Research output: Contribution to journalArticle

Abstract

Background: Atopic dermatitis is a chronic inflammatory condition with substantial burden and limited treatment options for adolescents with moderate-to-severe disease. Significantly more patients treated with dupilumab vs. placebo achieved Investigator’s Global Assessment 0/1 at week 16. Objective: The objective of this study was to assess the impact of dupilumab treatment vs. placebo on the achievement of clinically meaningful improvements in atopic dermatitis signs, symptoms and quality of life. Methods: R668-AD-1526 LIBERTY AD ADOL was a randomized, double-blinded, parallel-group, phase III clinical trial. Two hundred and fifty-one adolescents with moderate-to-severe atopic dermatitis received dupilumab 300 mg every 4 weeks (q4w; n = 84), dupilumab 200 or 300 mg every 2 weeks (q2w; n = 82), or placebo (n = 85). A post-hoc subgroup analysis was performed on 214 patients with Investigator’s Global Assessment > 1 at week 16. Measures of atopic dermatitis signs, symptoms, and quality of life were assessed. Clinically meaningful improvement in one or more of three domains of signs, symptoms, and quality of life was defined as an improvement of ≥ 50% in Eczema Area and Severity Index, ≥ 3 points in Peak Pruritus Numerical Rating Scale, or ≥ 6 points in the Children’s Dermatology Life Quality Index from baseline. Results: Of patients receiving dupilumab q2w, 80.5% [66/82] experienced clinically meaningful improvements in atopic dermatitis signs, symptoms, or quality of life at week 16 (vs. placebo, 20/85 [23.5%], difference 57.0% [95% confidence interval 44.5–69.4]; q4w vs. placebo, 53/84 [63.1%], difference 39.6% [95% confidence interval 25.9–53.3]; both p < 0.0001). Results were similar in adolescents with Investigator’s Global Assessment > 1 at week 16 (q2w, 46/62 [74.2%] vs. placebo, 18/83 [21.7%], difference 52.5% [95% confidence interval 38.5–66.6]; q4w, 38/69 [55.1%] vs. placebo, difference 33.4% [95% confidence interval 18.7–48.1]; both p < 0.0001). Conclusions: Dupilumab provided clinically meaningful improvements in signs, symptoms, and quality of life in adolescents with moderate-to-severe atopic dermatitis among patients with Investigator’s Global Assessment > 1 at week 16. Treatment responses should be interpreted in the context of such clinically relevant patient-reported outcome measures. Trial Registration: ClinicalTrials.gov; NCT03054428. Video abstract: [MediaObject not available: see fulltext.].

Original languageEnglish (US)
JournalAmerican Journal of Clinical Dermatology
DOIs
StateAccepted/In press - Jan 1 2019

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Atopic Dermatitis
Randomized Controlled Trials
Placebos
Quality of Life
Signs and Symptoms
Confidence Intervals
Research Personnel
Phase III Clinical Trials
Eczema
Pruritus
Dermatology
SAR231893
Therapeutics

ASJC Scopus subject areas

  • Dermatology

Cite this

Clinically Meaningful Responses to Dupilumab in Adolescents with Uncontrolled Moderate-to-Severe Atopic Dermatitis : Post-hoc Analyses from a Randomized Clinical Trial. / Paller, Amy S.; Bansal, Ashish; Simpson, Eric L.; Boguniewicz, Mark; Blauvelt, Andrew; Siegfried, Elaine C.; Guttman-Yassky, Emma; Hultsch, Thomas; Chen, Zhen; Mina-Osorio, Paola; Lu, Yufang; Rossi, Ana B.; He, Xinyi; Kamal, Mohamed; Graham, Neil M.H.; Pirozzi, Gianluca; Ruddy, Marcella; Eckert, Laurent; Gadkari, Abhijit.

In: American Journal of Clinical Dermatology, 01.01.2019.

Research output: Contribution to journalArticle

Paller, AS, Bansal, A, Simpson, EL, Boguniewicz, M, Blauvelt, A, Siegfried, EC, Guttman-Yassky, E, Hultsch, T, Chen, Z, Mina-Osorio, P, Lu, Y, Rossi, AB, He, X, Kamal, M, Graham, NMH, Pirozzi, G, Ruddy, M, Eckert, L & Gadkari, A 2019, 'Clinically Meaningful Responses to Dupilumab in Adolescents with Uncontrolled Moderate-to-Severe Atopic Dermatitis: Post-hoc Analyses from a Randomized Clinical Trial', American Journal of Clinical Dermatology. https://doi.org/10.1007/s40257-019-00478-y
Paller, Amy S. ; Bansal, Ashish ; Simpson, Eric L. ; Boguniewicz, Mark ; Blauvelt, Andrew ; Siegfried, Elaine C. ; Guttman-Yassky, Emma ; Hultsch, Thomas ; Chen, Zhen ; Mina-Osorio, Paola ; Lu, Yufang ; Rossi, Ana B. ; He, Xinyi ; Kamal, Mohamed ; Graham, Neil M.H. ; Pirozzi, Gianluca ; Ruddy, Marcella ; Eckert, Laurent ; Gadkari, Abhijit. / Clinically Meaningful Responses to Dupilumab in Adolescents with Uncontrolled Moderate-to-Severe Atopic Dermatitis : Post-hoc Analyses from a Randomized Clinical Trial. In: American Journal of Clinical Dermatology. 2019.
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title = "Clinically Meaningful Responses to Dupilumab in Adolescents with Uncontrolled Moderate-to-Severe Atopic Dermatitis: Post-hoc Analyses from a Randomized Clinical Trial",
abstract = "Background: Atopic dermatitis is a chronic inflammatory condition with substantial burden and limited treatment options for adolescents with moderate-to-severe disease. Significantly more patients treated with dupilumab vs. placebo achieved Investigator’s Global Assessment 0/1 at week 16. Objective: The objective of this study was to assess the impact of dupilumab treatment vs. placebo on the achievement of clinically meaningful improvements in atopic dermatitis signs, symptoms and quality of life. Methods: R668-AD-1526 LIBERTY AD ADOL was a randomized, double-blinded, parallel-group, phase III clinical trial. Two hundred and fifty-one adolescents with moderate-to-severe atopic dermatitis received dupilumab 300 mg every 4 weeks (q4w; n = 84), dupilumab 200 or 300 mg every 2 weeks (q2w; n = 82), or placebo (n = 85). A post-hoc subgroup analysis was performed on 214 patients with Investigator’s Global Assessment > 1 at week 16. Measures of atopic dermatitis signs, symptoms, and quality of life were assessed. Clinically meaningful improvement in one or more of three domains of signs, symptoms, and quality of life was defined as an improvement of ≥ 50{\%} in Eczema Area and Severity Index, ≥ 3 points in Peak Pruritus Numerical Rating Scale, or ≥ 6 points in the Children’s Dermatology Life Quality Index from baseline. Results: Of patients receiving dupilumab q2w, 80.5{\%} [66/82] experienced clinically meaningful improvements in atopic dermatitis signs, symptoms, or quality of life at week 16 (vs. placebo, 20/85 [23.5{\%}], difference 57.0{\%} [95{\%} confidence interval 44.5–69.4]; q4w vs. placebo, 53/84 [63.1{\%}], difference 39.6{\%} [95{\%} confidence interval 25.9–53.3]; both p < 0.0001). Results were similar in adolescents with Investigator’s Global Assessment > 1 at week 16 (q2w, 46/62 [74.2{\%}] vs. placebo, 18/83 [21.7{\%}], difference 52.5{\%} [95{\%} confidence interval 38.5–66.6]; q4w, 38/69 [55.1{\%}] vs. placebo, difference 33.4{\%} [95{\%} confidence interval 18.7–48.1]; both p < 0.0001). Conclusions: Dupilumab provided clinically meaningful improvements in signs, symptoms, and quality of life in adolescents with moderate-to-severe atopic dermatitis among patients with Investigator’s Global Assessment > 1 at week 16. Treatment responses should be interpreted in the context of such clinically relevant patient-reported outcome measures. Trial Registration: ClinicalTrials.gov; NCT03054428. Video abstract: [MediaObject not available: see fulltext.].",
author = "Paller, {Amy S.} and Ashish Bansal and Simpson, {Eric L.} and Mark Boguniewicz and Andrew Blauvelt and Siegfried, {Elaine C.} and Emma Guttman-Yassky and Thomas Hultsch and Zhen Chen and Paola Mina-Osorio and Yufang Lu and Rossi, {Ana B.} and Xinyi He and Mohamed Kamal and Graham, {Neil M.H.} and Gianluca Pirozzi and Marcella Ruddy and Laurent Eckert and Abhijit Gadkari",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s40257-019-00478-y",
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TY - JOUR

T1 - Clinically Meaningful Responses to Dupilumab in Adolescents with Uncontrolled Moderate-to-Severe Atopic Dermatitis

T2 - Post-hoc Analyses from a Randomized Clinical Trial

AU - Paller, Amy S.

AU - Bansal, Ashish

AU - Simpson, Eric L.

AU - Boguniewicz, Mark

AU - Blauvelt, Andrew

AU - Siegfried, Elaine C.

AU - Guttman-Yassky, Emma

AU - Hultsch, Thomas

AU - Chen, Zhen

AU - Mina-Osorio, Paola

AU - Lu, Yufang

AU - Rossi, Ana B.

AU - He, Xinyi

AU - Kamal, Mohamed

AU - Graham, Neil M.H.

AU - Pirozzi, Gianluca

AU - Ruddy, Marcella

AU - Eckert, Laurent

AU - Gadkari, Abhijit

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Atopic dermatitis is a chronic inflammatory condition with substantial burden and limited treatment options for adolescents with moderate-to-severe disease. Significantly more patients treated with dupilumab vs. placebo achieved Investigator’s Global Assessment 0/1 at week 16. Objective: The objective of this study was to assess the impact of dupilumab treatment vs. placebo on the achievement of clinically meaningful improvements in atopic dermatitis signs, symptoms and quality of life. Methods: R668-AD-1526 LIBERTY AD ADOL was a randomized, double-blinded, parallel-group, phase III clinical trial. Two hundred and fifty-one adolescents with moderate-to-severe atopic dermatitis received dupilumab 300 mg every 4 weeks (q4w; n = 84), dupilumab 200 or 300 mg every 2 weeks (q2w; n = 82), or placebo (n = 85). A post-hoc subgroup analysis was performed on 214 patients with Investigator’s Global Assessment > 1 at week 16. Measures of atopic dermatitis signs, symptoms, and quality of life were assessed. Clinically meaningful improvement in one or more of three domains of signs, symptoms, and quality of life was defined as an improvement of ≥ 50% in Eczema Area and Severity Index, ≥ 3 points in Peak Pruritus Numerical Rating Scale, or ≥ 6 points in the Children’s Dermatology Life Quality Index from baseline. Results: Of patients receiving dupilumab q2w, 80.5% [66/82] experienced clinically meaningful improvements in atopic dermatitis signs, symptoms, or quality of life at week 16 (vs. placebo, 20/85 [23.5%], difference 57.0% [95% confidence interval 44.5–69.4]; q4w vs. placebo, 53/84 [63.1%], difference 39.6% [95% confidence interval 25.9–53.3]; both p < 0.0001). Results were similar in adolescents with Investigator’s Global Assessment > 1 at week 16 (q2w, 46/62 [74.2%] vs. placebo, 18/83 [21.7%], difference 52.5% [95% confidence interval 38.5–66.6]; q4w, 38/69 [55.1%] vs. placebo, difference 33.4% [95% confidence interval 18.7–48.1]; both p < 0.0001). Conclusions: Dupilumab provided clinically meaningful improvements in signs, symptoms, and quality of life in adolescents with moderate-to-severe atopic dermatitis among patients with Investigator’s Global Assessment > 1 at week 16. Treatment responses should be interpreted in the context of such clinically relevant patient-reported outcome measures. Trial Registration: ClinicalTrials.gov; NCT03054428. Video abstract: [MediaObject not available: see fulltext.].

AB - Background: Atopic dermatitis is a chronic inflammatory condition with substantial burden and limited treatment options for adolescents with moderate-to-severe disease. Significantly more patients treated with dupilumab vs. placebo achieved Investigator’s Global Assessment 0/1 at week 16. Objective: The objective of this study was to assess the impact of dupilumab treatment vs. placebo on the achievement of clinically meaningful improvements in atopic dermatitis signs, symptoms and quality of life. Methods: R668-AD-1526 LIBERTY AD ADOL was a randomized, double-blinded, parallel-group, phase III clinical trial. Two hundred and fifty-one adolescents with moderate-to-severe atopic dermatitis received dupilumab 300 mg every 4 weeks (q4w; n = 84), dupilumab 200 or 300 mg every 2 weeks (q2w; n = 82), or placebo (n = 85). A post-hoc subgroup analysis was performed on 214 patients with Investigator’s Global Assessment > 1 at week 16. Measures of atopic dermatitis signs, symptoms, and quality of life were assessed. Clinically meaningful improvement in one or more of three domains of signs, symptoms, and quality of life was defined as an improvement of ≥ 50% in Eczema Area and Severity Index, ≥ 3 points in Peak Pruritus Numerical Rating Scale, or ≥ 6 points in the Children’s Dermatology Life Quality Index from baseline. Results: Of patients receiving dupilumab q2w, 80.5% [66/82] experienced clinically meaningful improvements in atopic dermatitis signs, symptoms, or quality of life at week 16 (vs. placebo, 20/85 [23.5%], difference 57.0% [95% confidence interval 44.5–69.4]; q4w vs. placebo, 53/84 [63.1%], difference 39.6% [95% confidence interval 25.9–53.3]; both p < 0.0001). Results were similar in adolescents with Investigator’s Global Assessment > 1 at week 16 (q2w, 46/62 [74.2%] vs. placebo, 18/83 [21.7%], difference 52.5% [95% confidence interval 38.5–66.6]; q4w, 38/69 [55.1%] vs. placebo, difference 33.4% [95% confidence interval 18.7–48.1]; both p < 0.0001). Conclusions: Dupilumab provided clinically meaningful improvements in signs, symptoms, and quality of life in adolescents with moderate-to-severe atopic dermatitis among patients with Investigator’s Global Assessment > 1 at week 16. Treatment responses should be interpreted in the context of such clinically relevant patient-reported outcome measures. Trial Registration: ClinicalTrials.gov; NCT03054428. Video abstract: [MediaObject not available: see fulltext.].

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