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. Adolescents with atopic dermatitis: does dupilumab improve their signs, symptoms, and quality of life? (MP4 212916 kb).

Conflict of interest statement

Amy S. Paller has served as an investigator and/or consultant for AbbVie, Amgen, AnaptysBio, Asana, Dermavant, Dermira, Eli Lilly, Galderma, Forte, Incyte, Janssen, LEO Pharma, Matrisys Bioscience, Menlo Therapeutics, MorphoSys/Galapagos, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., and Sanofi. Ashish Bansal, Zhen Chen, Paola Mina-Osorio, Yufang Lu, Xinyi He, Mohamed Kamal, Neil M. H. Graham, Marcella Ruddy, and Abhijit Gadkari are employees and shareholders of Regeneron Pharmaceuticals, Inc. Eric L. Simpson served as an investigator and/or consultant for AbbVie, Boehringer Ingelheim, Dermavant, Eli Lilly, Galderma, Forte, Incyte, Kyowa Hakko Kirin, LEO Pharma, Merck, Menlo Therapeutics, Pfizer, Pierre Fabre Dermo Cosmetique, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, and Valeant. Mark Boguniewicz served as an investigator and/or consultant for Regeneron Pharmaceuticals, Inc. and Sanofi Genzyme. Andrew Blauvelt served as a consultant and investigator for AbbVie, Aclaris, Akros, Allergan, Almirall, Amgen, Arena, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, Genentech/Roche, GlaxoSmithKline, Janssen, LEO Pharma, Meiji, Merck Sharp & Dohme, Novartis, Pfizer, Purdue Pharma, Regeneron Pharmaceuticals, Inc., Revance, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, UCB Pharma, Valeant, and Vidac and served as a speaker for Janssen, Regeneron Pharmaceuticals, Inc., and Sanofi Genzyme. Elaine C. Siegfried served as a principal investigator for AbbVie, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly, LEO Pharma, Novan, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, and UCB and as an investigator for Allergan, Eli Lilly, Janssen, Mayne, Regeneron Pharmaceuticals, Inc., and Verrica. Emma Guttman-Yassky served as an investigator for AbbVie, Celgene, Eli Lilly, Galderma, GlaxoSmithKline, Glenmark, LEO Pharma, Pfizer, Regeneron Pharmaceuticals, Inc., and Sanofi; as a consultant for AbbVie, Anacor, Asana Biosciences, Daiichi Sankyo, DBV Technologies, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Glenmark, Kiniksa, Kyowa, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Realm, Regeneron Pharmaceuticals, Inc., and Sanofi and received research support from AbbVie, Celgene, Dermira, Galderma, Innovaderm, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., and Sanofi. Thomas Hultsch, Ana B. Rossi, Gianluca Pirozzi, and Laurent Eckert are employees of Sanofi, and own Sanofi stock/stock options.

Figures

Fig. 1

Proportions of patients in the full analysis set (FAS) who achieved clinically meaningful improvements in signs, symptoms, and quality of life as defined by a 50% improvement from baseline in Eczema Area and Severity Index (EASI-50), b Peak Pruritus Numerical Rating Scale (NRS) ≥ 3-point improvement from baseline, c Children’s Dermatology Life Quality Index (CDLQI) ≥ 6-point improvement from baseline, and d EASI-50 or Peak Pruritus NRS ≥ 3-point improvement from baseline or CDLQI ≥ 6-point improvement from baseline. ap < 0.01 vs. placebo, bp < 0.05 vs. placebo, q2w every 2 weeks, q4w every 4 weeks

Fig. 2

Proportions of patients in the full analysis set (FAS) who achieved clinically relevant thresholds for improvements in signs, symptoms, and/or quality of life (defined as 50% improvement from baseline in Eczema Area and Severity Index [EASI-50] or ≥ 3-point improvement from baseline in Peak Pruritus Numerical Rating Scale (NRS) score or ≥ 6-point improvement from baseline in Children’s Dermatology Life Quality Index [CDLQI]) at week 16. q2w every 2 weeks, q4w every 4 weeks

Fig. 3

Proportions of patients in the Investigator’s Global Assessment (IGA) > 1 subgroup who achieved clinically meaningful improvements in signs, symptoms, and quality of life as defined by a 50% improvement from baseline in Eczema Area and Severity Index (EASI-50), b Peak Pruritus Numerical Rating Scale (NRS) ≥ 3-point improvement from baseline, c Children’s Dermatology Life Quality Index (CDLQI) ≥ 6-point improvement from baseline, and d EASI-50 or Peak Pruritus NRS ≥ 3-point improvement from baseline or CDLQI ≥ 6-point improvement from baseline. ap < 0.01 vs. placebo, bp < 0.05 vs. placebo, q2w every 2 weeks, q4w every 4 weeks