Abstract
Background: Children aged ≥ 6 to < 12 years with severe atopic dermatitis (AD) have limited treatment options. In a 16-week, randomized, placebo-controlled, phase III trial in children, dupilumab, a monoclonal antibody inhibiting interleukin (IL)-4/IL-13 signalling, significantly improved signs and symptoms with acceptable safety; longer-term safety and efficacy data are lacking. Objectives: To report the pharmacokinetic profile and long-term safety and efficacy of dupilumab in children (aged ≥ 6 to < 12 years) with severe AD. Methods: Children (aged ≥ 6 to < 12 years) with severe AD were enrolled in a global, multicentre, phase IIa, open-label, ascending-dose, sequential cohort study and subsequent open-label extension (OLE) study. Patients received single-dose dupilumab 2 or 4 mg kg−1 followed by 8-week pharmacokinetic sampling, then 2 or 4 mg kg−1 weekly for 4 weeks (phase IIa), followed by the same weekly regimen (OLE). Primary endpoints were dupilumab concentration–time profile and treatment-emergent adverse events (TEAEs); secondary assessments included Eczema Area and Severity Index (EASI) and Peak Pruritus Numeric Rating Scale (PP-NRS) score. Results: Of 38 children enrolled, 37 completed phase IIa and 33 continued to the OLE. Nonlinear, target-mediated pharmacokinetics characterized dupilumab concentrations (week 24–48 mean serum concentrations: 2 mg kg−1, 61–77 mg L−1; 4 mg kg−1, 143–181 mg L−1). TEAEs were mostly mild to moderate and transient; none led to treatment discontinuation. The most commonly reported TEAEs were nasopharyngitis (2 mg kg−1, 47%; 4 mg kg−1, 56%) and AD exacerbation (29% and 13%, respectively). Single-dose dupilumab rapidly improved AD with further improvements through week 52. Mean EASI and PP-NRS improved by −37%/−33% and −17%/−20% at week 2 (phase IIa) and −92%/−84% and −70%/−58% at week 52 (OLE), respectively. Conclusions: These safety and efficacy results support the use of dupilumab as a continuous long-term treatment for children aged ≥ 6 to < 12 years with severe AD.
| Original language | English |
|---|---|
| Journal | British Journal of Dermatology |
| ISSN | 0007-0963 |
| DOIs | |
| Publication status | Published - 24.09.2020 |
Funding
This research was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. The study sponsors participated in the study design; collection, analysis and interpretation of the data; writing of the report and the decision to submit the article for publication. The authors acknowledge Shikha Bansal, Erika Culotta, Elizabeth Bucknam, John D. Davis, Jennifer Foy, Jacqueline Kuritzky, Deirdre Mulhearn, Nelson Rita, George Vlamis and Linda Williams from Regeneron Pharmaceuticals, Inc. and Leda Mannent, Nicolas Duverger, Christine Xu, Elizabeth Laws, El‐Bdaoui Haddad, and Adriana Mello from Sanofi for their contributions. Conflicts of interest. M.J.C. has acted as an investigator and consultant for AbbVie, Astellas, Boots, Dermavant, Galapagos, Galderma, Hyphens Pharma, Johnson & Johnson, LEO Pharma, L’Oréal, Menlo Therapeutics, Novartis, Oxagen, Pfizer, Procter & Gamble, Reckitt Benckiser, Regeneron Pharmaceuticals, Inc. and Sanofi Genzyme. D.T. has received research support from AbbVie, Almirall, DS‐Biopharma, Eli Lilly, Galapagos, Galderma, LEO Pharma, MorphoSys, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi and independent advisor honoraria from AbbVie and Novartis. D.T. has been a consultant for AbbVie, Beiersdorf, DS‐Biopharma, Galapagos, MorphoSys, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi and received advisory board honoraria from AbbVie, Eli Lilly, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc. and Sanofi. L.F.E has received consultant honoraria from AbbVie, Almirall, BMS, Dermira, Dermavant, Eli Lilly, Galderma, Incyte, MatriSys Bioscience, Novartis, Otsuka, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme and Valeant/Ortho Derm and study support (to institution) from BMS, Dermira, Dermavant, Eli Lilly, Galderma, Incyte, Medimetriks, Pfizer, Regeneron Pharmaceuticals, Inc. and Sanofi Genzyme, Valeant. P.D.A. received advisory board and project grant funding from Sanofi Genzyme. X.S., Z.C., B.A., M.P.K., M.A.K. and A.B. are employees and shareholders of Regeneron Pharmaceuticals, Inc. S.B. and N.M.H.G. are former employees and shareholders of Regeneron Pharmaceuticals, Inc. I.G., J.T.O’M. and N.P. are employees of Sanofi and may hold stock and/or stock options in the company.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
