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.

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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.To report the pharmacokinetic profile and long-term safety and efficacy of dupilumab in children (aged ≥6 to <12 years) with severe AD.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.Of 38 children enrolled, 37 completed phase IIa, 33 continued to the OLE. Nonlinear, target-mediated 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.These safety and efficacy results support use of dupilumab as continuous long-term treatment for children aged ≥6 to <12 years with severe AD.


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