Dupilumab Provides Acceptable Safety and Sustained Efficacy for up to 4 Years in an Open-Label Study of Adults with Moderate-to-Severe Atopic Dermatitis

Abstract

Background: Moderate-to-severe atopic dermatitis (AD) often requires long-term management with systemic therapies.

Objective: Our objective was to report the safety and efficacy of dupilumab treatment up to 4 years in adults with moderate-to-severe AD and efficacy in a subgroup of patients who transitioned from dupilumab once-weekly (qw) to administration every other week (q2w).

Methods: This interim analysis of the open-label extension study (NCT01949311) evaluated dupilumab 300 mg qw or q2w in adults previously enrolled in dupilumab trials for moderate-to-severe AD. Patients switched from qw to q2w following protocol amendment. The primary outcome was safety; efficacy was also assessed.

Results: Of 2677 patients enrolled and treated, 352 (13.1%) completed week 204 (end of efficacy assessments) and 202 (7.5%) completed safety follow-up through week 244. Self-reported compliance was 98.1%. Dupilumab's safety profile was consistent with previous reports. Common treatment-emergent adverse events (≥5%) included nasopharyngitis, AD, upper respiratory tract infection, oral herpes, conjunctivitis, injection-site reaction, and headache. At week 204, mean ± standard deviation (SD) Eczema Area and Severity Index was 2.46 ± 3.98, and mean percent change from parent study baseline (PSBL) was -91.07%; mean ± SD Pruritus Numerical Rating Scale score was 2.10 ± 1.83, and mean percent change from PSBL was -68.74%. Efficacy was maintained in patients (n = 226) who transitioned from qw to q2w dosing. Limitations of this study included its open-label design, the lack of control arm, and smaller subsets of patients at later timepoints and receiving the approved q2w regimen.

Conclusion: These results support dupilumab as continuous long-term treatment for adults with moderate-to-severe AD; efficacy was sustained following transition from qw to q2w dosing. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT01949311.

Conflict of interest statement

Lisa A. Beck has acted as investigator and/or consultant for AbbVie, Allakos, Arena Pharmaceuticals, AstraZeneca, BenevolentAI, DermTech, Galderma, Inc., Incyte, Janssen, Kiniksa Pharmaceuticals, LEO Pharma, Lilly, Novartis, Numab Therapeutics, Pfizer, Principia Biopharma, RAPT Therapeutics, Regeneron Pharmaceuticals, Ribon Therapeutics, Sanofi, sanofi-aventis, Stealth BioTherapeutics, and Union Therapeutics; and owns stock in 3M, Gilead, Medtronics, and Moderna. Mette Deleuran has received research support, honoraria for lecturing, and/or consulting/advisory board agreements from AbbVie, Arena Pharmaceuticals, Aslan Pharmaceuticals, Eli Lilly, Incyte, La Roche-Posay, LEO Pharma, MSD, Numab Therapeutics, Pierre Fabre, Pfizer, Regeneron Pharmaceuticals, Inc., and Sanofi. Robert Bissonnette has acted as a consultant for and/or has received grants/research support from AbbVie, Arcutis Biotherapeutics, Arena Pharmaceuticals, Aristea Therapeutics, Asana BioSciences, Bellus Health, Bluefin Biomedicine, Boehringer Ingelheim, Cara Therapeutics, Dermavant, Eli Lilly, EMD Serono, Evidera, Galderma, GSK, Inmagene Biopharmaceuticals, Incyte, Kiniksa Pharmaceuticals, Kyowa Kirin, LEO Pharma, Novan, Pfizer, Ralexar Therapeutics, RAPT Therapeutics, Regeneron Pharmaceuticals, Inc., Respivant Sciences, Sanofi, Siena Biopharmaceuticals, Target RWE, and Vyne Therapeutics and is a shareholder with Innovaderm Research. Marjolein de Bruin-Weller has acted as a consultant, advisory board member, and/or speaker for AbbVie, Almirall, Arena Pharmaceuticals, Aslan Pharmaceuticals, Eli Lilly, Galderma, Janssen, LEO Pharma, Pfizer, Regeneron Pharmaceuticals, Inc. Ryszard Galus has acted as principal investigator for Boehringer Ingelheim, Dermira, Galderma, Glenmark, Incyte, LEO Pharma, Pfizer, Regeneron Pharmaceuticals, Inc., and Sanofi. Takeshi Nakahara has received speaker fees from Maruho and Sanofi. Seong Jun Seo has acted as speaker, investigator, and consultant for AbbVie, Eli Lilly, LEO Pharma, Sanofi. Faisal Khokhar, Jing Xiao, Noah Levit, and Arsalan Shabbir are employees and shareholders or Regeneron Pharmaceuticals, Inc. Jignesh Vakil, Ainara Rodriguez Marco, John O’Malley are employees of and may hold stock and/or stock options in Sanofi.

© 2022. The Author(s).

Figures

Fig. 1

Study flow diagram

Fig. 2

Percentage of patients achieving ≥50%, ≥75%, and ≥90% improvement in Eczema Area and Severity Index (EASI-50, EASI-75 and EASI-90, respectively) over time

Fig. 3

Mean EASI over time. *Uptick because of patient re-entry to the study at week 156. BL baseline, EASI Eczema Area and Severity Index, LOCF last observation carried forward, OC observed cohort, PSBL parent study baseline, SE standard error

Fig. 4

Mean weekly Pruritus NRS score over time. *Uptick because of patient re-entry to the study at week 156. BL baseline, LOCF last observation carried forward, NRS Numerical Rating Scale, OC observed cohort, PSBL parent study baseline, SE standard error

Fig. 5

Mean A EASI and B Pruritus NRS score of patients switched from dupilumab 300 weekly to 300 every 2 weeks. Baseline of every 2 weeks dosing is defined as last assessment on weekly dose. Vertical bars represent the minimum and maximum values. EASI Eczema Area and Severity Index, NRS Numerical Rating Scale

Fig. 6

Kaplan–Meier curve of continuous maintenance of NRS score ≤4 or EASI ≤7 following dupilumab dose switch from 300 mg weekly to 300 mg q2w. Patients maintained response (treated >24 weeks or not) as censored at last assessment within 24 weeks of dose switch. EASI Eczema Area and Severity Index, NRS Numerical Rating Scale, q2w every 2 weeks