Dupilumab provides favourable long-term safety and efficacy in children aged ≥ 6 to < 12 years with uncontrolled, severe atopic dermatitis: results from an open-label phase IIa study and subsequent phase III open-label extension study

M. J. Cork, D. Thaçi, L. F. Eichenfield, Peter Arkwright, X. Sun, Z. Chen, B. Akinlade, S. Boklage, I. Guillemin, M. P. Kosloski, M. A. Kamal, J. T. O'Malley, N. Patel, N. M. H. Graham, A. Bansal

Research output: Contribution to specialist publicationArticle

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 signaling, 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 followed by 8-week pharmacokinetic sampling, then 2 or 4 mg/kg 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, 33 continued to the OLE. Nonlinear, targetmediated pharmacokinetics characterized dupilumab concentrations (week24-48 mean serum concentrations: 2 mg/kg:61–77 mg/L; 4 mg/kg:143–181 mg/L). TEAEs were mostly mild to moderate and transient; none led to treatment discontinuation. Most commonly reported TEAEs were nasopharyngitis (2 mg/kg:47%; 4 mg/kg:56%) and AD exacerbation (29%/13%). Single-dose dupilumab rapidly improved AD with further improvements through week52. Mean EASI and PP-NRS improved by −37%/−33% and −17%/−20% at week2 (phase IIa) and −92%/−84% and −70%/−58% at week52 (OLE), respectively. Conclusions: These safety and efficacy results support use of dupilumab as continuous long-term treatment for children aged ≥6 to <12 years with severe AD.
Original languageEnglish
Specialist publicationBritish Journal of Dermatology
Publication statusAccepted/In press - 3 Aug 2020

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