Original article
Dupilumab therapy provides clinically meaningful improvement in patient-reported outcomes (PROs): A phase IIb, randomized, placebo-controlled, clinical trial in adult patients with moderate to severe atopic dermatitis (AD)

https://doi.org/10.1016/j.jaad.2016.04.054Get rights and content

Background

Moderate to severe atopic dermatitis (AD) is associated with substantial patient burden despite current therapies.

Objective

We sought to evaluate dupilumab treatment on patient-reported outcomes in adults with moderate to severe AD.

Methods

Adults (N = 380) with moderate to severe AD inadequately controlled by topical medications were randomized to 16 weeks of double-blind, subcutaneous treatment with dupilumab 100 mg every 4 weeks, 200 mg every 2 weeks, 300 mg every 2 weeks, 300 mg once weekly, or placebo. Patient-reported outcomes included pruritus numeric rating scale; patient-reported sleep item on Scoring AD scale; Patient-Oriented Eczema Measure; Hospital Anxiety and Depression Scale; Dermatology Life Quality Index; and 5-dimension 3-level EuroQol.

Results

Dupilumab reduced peak itch at 16 weeks relative to placebo by 1.1 to 3.2 points on numeric rating scale (P < .0001 all doses, except 100 mg every 4 weeks P < .05); improved sleep and health-related quality of life on Dermatology Life Quality Index and 5-dimension 3-level EuroQol (P < .05 all doses, except 100 mg every 4 weeks); and reduced anxiety and depression symptoms (P < .05 all doses). Dupilumab's effects appeared early and achieved clinically relevant improvements without significant safety concerns.

Limitations

There are potential cultural differences affecting patient-reported outcome responses. Outcomes were secondary or exploratory end points.

Conclusion

Dupilumab produced early and sustained patient-reported and clinically relevant improvements in sleep, mental health, and health-related quality of life; the two 300-mg dose regimens resulted in greatest benefits.

Section snippets

Study design

This was an international, randomized, placebo-controlled, double-blind, parallel group dose-ranging study; complete details of study design and methods along with primary results of changes in objective disease and full safety analysis have been previously reported.13 ClinicalTrials.gov registration number is NCT01859988 and EudraCT number is 2012-003651-11. The protocol was approved by the appropriate institutional review boards/ethics committees at each study site. All patients provided

Patients

Of 452 patients assessed for eligibility, 380 were randomized and 379 received 1 or more doses of study treatment (placebo, n = 61; dupilumab, n = 318). Among these patients, 86.9% and 92.2% in the placebo and dupilumab groups, respectively, completed the 16-week treatment period. Baseline demographic and clinical characteristics were similar among treatments (Table II).

Itch and other skin symptoms

Relative to placebo, dupilumab significantly reduced itch (daily peak pruritus NRS weekly average) from baseline at week 16 in

Discussion

This analysis complements those previously reported on physician-assessed clinical outcomes13 and provides evidence that dupilumab results in clinically relevant improvements in itch, sleep, mental health, HRQoL, and overall health status in adults with moderate to severe AD. These results are noteworthy because patients in this study had persistent moderate to severe AD despite a high reliance on topical and systemic treatments, and were characterized by a substantial disease burden at study

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    Supported by Sanofi and Regeneron Pharmaceuticals Inc. Medical writing support was provided by E. Jay Bienen, funded by Sanofi and Regeneron Pharmaceuticals Inc. The authors are responsible for all content and editorial decisions and received no honoraria related to the development of this publication.

    Disclosure: Dr Simpson received grants/research support from Amgen, Celgene, Chugai, Galderma, and Regeneron Pharmaceuticals Inc, and is a consultant for Anacor, Asubio, Celgene, Galderma, Genentech, Medicis, and Merck. Drs Gadkari, Wu, Ardeleanu, and Graham, and Ms Mastey are employees of and stockholders in Regeneron Pharmaceuticals Inc. Dr Worm received grants/research support from Celgene, Chugai, Galderma, and Regeneron Pharmaceuticals Inc. Dr Soong received honoraria for participation in advisory boards and speaker bureaus and research funding from Sanofi and Regeneron Pharmaceuticals Inc; received research funding from GSK, Genentech, AstraZeneca, and Teva; and received speaker fees from Teva, Meda, and Genentech. Dr Blauvelt is a scientific adviser and clinical study investigator for Amgen, AbbVie, Boehringer Ingelheim, Celgene, Dermira, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals Inc, and Sandoz. Drs Eckert, Pirozzi, and Sutherland are employees of and stockholders in Sanofi.

    This article is based on data previously presented at the American Academy of Allergy, Asthma, and Immunology Annual Meeting 2015 in Houston, TX, February 20-24, 2015.

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    © 2016 by the American Academy of Dermatology, Inc.