Dupilumab Provides Favorable Safety and Sustained Efficacy for up to 3 Years in an Open-Label Study of Adults with Moderate-to-Severe Atopic Dermatitis

Abstract

Background: Management of moderate-to-severe atopic dermatitis (AD) commonly requires long-term treatment.

Objective: The aim of this study was to report the safety and efficacy of dupilumab treatment for up to 3 years in adults with moderate-to-severe AD.

Methods: This ongoing, multicenter, open-label extension study (LIBERTY AD OLE; NCT01949311) assessed dupilumab treatment in adults previously enrolled in dupilumab trials. Patients received dupilumab 300 mg weekly up to 148 weeks. The primary outcome was safety.

Results: Of 2677 patients enrolled and treated, 347 reached week 148. Mean self-reported drug compliance was 98.2%. Safety data were consistent with previously reported trials (270.1 adverse events [AEs]/100 patient-years; 6.9 serious AEs/100 patient-years) and the known dupilumab safety profile. Common AEs (≥ 5% of patients) included nasopharyngitis, AD, upper respiratory tract infection, conjunctivitis, headache, oral herpes, and injection-site reactions. AD signs and symptoms showed sustained improvements during treatment with mean (standard deviation, mean percentage change from parent study baseline) Eczema Area and Severity Index 1.4 (3.2, - 95.4%) and weekly Pruritus Numerical Rating Scale 2.2 (1.8, - 65.4%) at week 148.

Limitations: No control arm; fewer patients at later time points; regimen different from the approved 300 mg every 2 weeks dose.

Conclusion: These safety and efficacy results support dupilumab as a continuous long-term treatment for adults with moderate-to-severe AD.

Trial registration: ClinicalTrials.gov: NCT01949311. Dupilumab provides favorable safety and sustained efficacy for up to 3 years in an open-label study of adults with moderate-to-severe atopic dermatitis (MP4 139831 kb).

Conflict of interest statement

Lisa A. Beck: AbbVie, LEO Pharma, Pfizer, Regeneron Pharmaceuticals, Inc.—investigator and consultant; Allakos, Arena Pharma, Astra Zeneca, LEO Pharma, Eli Lilly, Novan, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, UCB, Vimalan—consultant; Medtronics, Pfizer—stock owner. Diamant Thaçi: AbbVie, Almirall, Amgen, Asana Biosciences, Beiersdorf, Boehringer Ingelheim, Celgene, Dermira, DS Biopharma, Eli Lilly, Galapagos, Galderma, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Merck Sharp & Dohme, MorphoSys, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sandoz, Sanofi, Sun Pharma, UCB—consultant, advisory board member, and/or investigator. Mette Deleuran: AbbVie, Almirall, Eli Lilly, Galapagos, LEO Pharma, Meda Pharma, Pfizer, Pierre Fabre, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme—received research support and/or honoraria for lecturing, and consulting/advisory board agreements. Andrew Blauvelt: AbbVie, Aclaris, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dermira, Eli Lilly, FLX Bio, Forte, Galderma, Janssen, LEO Pharma, Novartis, Ortho Derm, Pfizer, Regeneron Pharmaceuticals, Inc., Sandoz, Sanofi Genzyme, Sun Pharma, UCB—scientific adviser and clinical study investigator; AbbVie—paid speaker. Robert Bissonnette: AbbVie, Aquinox Pharmaceuticals, Arcutis Antiobix, Asana Biosciences, Astellas, Boehringer Ingelheim, Brickell Biotech, Dermavant, Dermira, Dignity Sciences, Eli Lilly, Galderma, Glenmark, GlaxoSmithKline-Stiefel, Hoffman-La Roche, Kiniksa, Incyte, LEO Pharma, NeoKera, Pfizer, Ralexar Therapeutics, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, Vitae—consultant and/or has received grants/research support; Innovaderm Research—shareholder. Marjolein de Bruin-Weller: Regeneron Pharmaceuticals, Inc., Sanofi Genzyme—Principal Investigator, advisory board member, consultant; AbbVie—Principal Investigator, advisory board member; Pfizer, Eli Lilly, UCB—advisory board member. Michihiro Hide: Kaken Pharmaceutical, Kyorin Pharmaceutical, Kyowa Hakko Kirin, Maruho, MDS, Mitsubishi Tanabe Pharma, Sanofi KK, Taiho Pharma, Teikoku Seiyaku, Torii Pharmaceutical, Uriach—honoraria for lectures. Lawrence Sher: Aimmune, Optinose, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme—advisory board member; Regeneron Pharmaceuticals, Inc., Sanofi Genzyme—speaker fees; Aimmune, Amgen, Astra Zeneca, Circassia, DBV, Galderma, GlaxoSmithKline, Lupin, Merck, Mylan, Novartis, Novo Nordisk, Optinose, Pearl, Pfizer, Pulmagen, Roxane, Sanofi, Spirometrix, Teva, Vectura, Watson—clinical trials funding. Iftikhar Hussain: CSL Behring, Genentech, Optinose, Pfizer—advisory board member; AbbVie, AnaptysBio, Asana Biosciences, Astra Zeneca, CSL Behring, Genentech, GlaxoSmithKline, Gossamer Bio, HAL Allergy, Kiniksa Pharmaceuticals, LEO Pharma, Menlo Therapeutics, Merck, Novartis, Optinose, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Shire, Vanda—Principal Investigator. Zhen Chen, Faisal A. Khokhar, Bethany Beazley, Marcella Ruddy, Neil M.H. Graham, Marius Ardeleanu, Brad Shumel: Regeneron Pharmaceuticals, Inc.—employees and shareholders. Naimish Patel: Sanofi—employee, may hold stock and/or stock options in the company.

Figures

Fig. 1

Study flow diagram

Fig. 2

Mean EASI over time. *The relatively low patient number at week 148 resulted from the temporary removal of this assessment from the end-of-treatment visit with the adoption of Amendment 6 that was restored as of Amendment 7. BL baseline, EASI Eczema Area and Severity Index, LOCF last observation carried forward, MI multiple imputation, OC observed cohort, PSBL parent study baseline, SE standard error

Fig. 3

Mean weekly average Pruritus NRS over time. BL baseline, LOCF last observation carried forward, MI multiple imputation, NRS Numerical Rating Scale, OC observed cohort, PSBL parent study baseline, SE standard error