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Multicenter Study
. 2024 Aug 1;160(8):805-812.
doi: 10.1001/jamadermatol.2024.1536.

Dupilumab in Adults With Moderate to Severe Atopic Dermatitis: A 5-Year Open-Label Extension Study

Lisa A Beck  1 , Robert Bissonnette  2 , Mette Deleuran  3 , Takeshi Nakahara  4 , Ryszard Galus  5 , Anna Coleman  6 , Guy Gherardi  7 , Jing Xiao  8 , Robert Dingman  8 , Christine Xu  9 , Elena Avetisova  8 , Ariane Dubost-Brama  10 , Arsalan Shabbir  8
Affiliations
Multicenter Study

Dupilumab in Adults With Moderate to Severe Atopic Dermatitis: A 5-Year Open-Label Extension Study

Lisa A Beck et al. JAMA Dermatol. .

Abstract

Importance: Moderate to severe atopic dermatitis (AD) is a chronic inflammatory skin disease that often requires continuous long-term systemic management. Long-term safety and efficacy data for treatment options are critically important.

Objective: To assess the safety and efficacy of dupilumab treatment for up to 5 years in adults with moderate to severe AD.

Design, setting, and participants: The 5-year LIBERTY AD open-label extension study was conducted from September 2013 to June 2022 at 550 sites in 28 countries. The study enrolled adult patients with moderate to severe AD who had participated in previous dupilumab clinical trials. Data were analyzed from August 2022 to February 2023.

Exposures: At enrollment, patients initiated a regimen of subcutaneous dupilumab, 200 mg, weekly (400-mg loading dose). The regimen was amended in June 2014 to dupilumab, 300 mg, weekly (600-mg loading dose) based on a dose-ranging study and again in November 2019 to dupilumab, 300 mg, every 2 weeks to align with the regulatory regimen approvals.

Main outcomes and measures: The primary end points were the incidence and rate of treatment-emergent adverse events (TEAEs). Key secondary end points included incidence and rate of serious TEAEs and adverse events of special interest, proportion of patients achieving an Investigator's Global Assessment (IGA) score of 0 or 1 (clear or almost clear), and proportion of patients with 75% or more improvement in the Eczema Area and Severity Index (EASI) from the parent study baseline.

Results: A total of 2677 patients were enrolled and treated in the open-label extension study; 1611 (60.2%) were male, and the mean (SD) age was 39.2 (13.4) years. A total of 334 patients (12.5%) completed treatment up to week 260. The most common reasons for withdrawal were due to regulatory approval of dupilumab in compliance with the study protocol (810 of 1380 [58.7%]), patient withdrawal (248 of 1380 [18.0%]), and adverse events (116 of 1380 [8.4%]). Exposure-adjusted rates of TEAEs were generally stable or declined throughout the study. Common TEAEs (incidence of 5% or greater) included nasopharyngitis, worsening AD, upper respiratory tract infection, conjunctivitis, conjunctivitis allergic, headache, oral herpes, and injection-site reaction. At week 260, 220 of 326 patients (67.5%) achieved an IGA score of 0 or 1 and 288 of 324 (88.9%) achieved 75% or greater improvement in the EASI. The mean (SD) EASI score was 16.39 (14.60) at baseline and 2.75 (5.62) at end of study.

Conclusions and relevance: In this study, there was sustained safety and efficacy of continuous long-term dupilumab treatment for adults with moderate to severe AD.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Beck reported grants from Regeneron Pharmaceuticals Inc and Sanofi as well as manuscript writing for Excerpta Medica during the conduct of the study; personal fees from Regeneron Pharmaceuticals Inc and Sanofi outside the submitted work; is a consultant for AbbVie, Allakos, Arcutis Biotherapeutics, Arena Pharmaceuticals, Dermavent, DermTech, Escient Pharma, Eli Lilly, Evelo Biosciences, Galderma, Incyte, Janssen, LEO Pharma, Merck, Nektar Therapeutics, Numab Therapeutics, Pfizer, RAPT Therapeutics, Regeneron Pharmaceuticals Inc, Ribon Therapeutics, Sanofi Genzyme, Sanofi-Aventis, Stealth BioTherapeutics, Trevi Therapeutics, Union Therapeutics, and Xencor; and has been an investigator for trials funded by AbbVie, AstraZeneca, DermTech, Kiniksa, Pfizer, Regeneron Pharmaceuticals Inc, Ribon Therapeutics, and Sanofi. Dr Bissonnette reported grants from AbbVie, Amgen, Arcutis, Bellus, BioMimetix, Cara Therapeutics, Clexio, Dermavant, Escient, Fresh Tracks, Incyte, Janssen, LEO Pharma, Merck, Opsidio, Pfizer, Target RWE, Vyne Therapeutics, and Xencor; consultation to AbbVie, Amgen, Apogee, Arcutis, Asana, Bluefin, Boehringer Ingelheim, Boston Pharma, Dermavant, Eli Lilly, Escient, Evidera, Galderma, GlaxoSmithKline, Incyte, Janssen, LEO Pharma, Novartis, Pfizer, RAPT Therapeutics, Sanofi Genzyme, Sanofi-Aventis, and Target RWE; and was a shareholder in Innovaderm Research during the conduct of the study. Dr Deleuran reported personal fees from Sanofi Genzyme and Regeneron Pharmaceuticals Inc during the conduct of the study as well as personal fees from AbbVie, Almirall, Arena Pharmaceuticals, Aslan Pharmaceuticals, Eli Lilly, Incyte, Kymab, LEO Pharma, Mustela, Numab, Pfizer, and Pierre Fabre outside the submitted work. Dr Nakahara reported personal fees from AbbVie, Eli Lilly, Otsuka, Pfizer, Sanofi, and Sun Pharma during the conduct of the study. Dr Galus reported personal fees from Synexus and has been an investigator for trials funded by Chugai, Galderma, Glenmark, Incyte, Kymab, Pfizer, Regeneron Pharmaceuticals Inc, and Sanofi outside the submitted work. Dr Coleman is a shareholder in Regeneron Pharmaceuticals Inc. Dr Gherardi is a shareholder in Sanofi. Dr Dubost-Brama is a shareholder in Sanofi. Dr Shabbir is a shareholder in Regeneron Pharmaceuticals Inc. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Flow Diagram
aStudy duration varied based on country of enrollment and the protocol amendment to which patients consented. A total of 2390 consented to up to 3 years of treatment and 384 consented to up to 5 years of treatment. bDue to regulatory approval/commercial availability of dupilumab in compliance with study protocol. cIncludes relocation, desire for pregnancy, did not want to discontinue treatment for 12 weeks, work/school conflict, and personal reasons not specified. dIncludes patients withdrawn from the study, both those receiving treatment at the time of withdrawal and those not receiving treatment during the safety follow-up period.
Figure 2.
Figure 2.. Investigator’s Global Assessment Score of 0 or 1 Over Time
aFollowing protocol amendments in June 2017 and January 2018, 113 and 272 patients, respectively, re-entered the trial, with 102 and 207 patients having a treatment interruption of more than 8 weeks between study weeks 148 and 164.
Figure 3.
Figure 3.. Improvement in Eczema Area and Severity Index (EASI) Score Over Time
aFollowing protocol amendments in June 2017 and January 2018, 113 and 272 patients, respectively, re-entered the trial, with 102 and 207 patients having a treatment interruption of more than 8 weeks between study weeks 148 and 164. bAll study days beyond 1794 days (week 260 and beyond) are included; study day is calculated relative to the date of first study drug injection.
See this image and copyright information in PMC

References

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