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BackgroundChildren 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.ObjectivesTo report the pharmacokinetic profile and long-term safety and efficacy of dupilumab in children (aged ≥ 6 to < 12 years) with severe AD.MethodsChildren (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.ResultsOf 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.ConclusionsThese 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.

Background Skin barrier dysfunction precedes eczema development. We tested whether daily emollient in the first year can prevent eczema in high-risk children. Methods We conducted a UK, multicentre, pragmatic, 2-arm, parallel-group randomised controlled trial. Term newborns with family history of atopic disease were randomised (1:1) to apply emollient daily (Diprobase cream® or DoubleBase® gel®) for the first year plus standard skin-care advice (emollient group) or standard skin-care advice only (controls). Research nurses assessing outcomes at 2-years were masked to allocation. Primary outcome was eczema at 2 years (UK working party criteria) with analysis as randomised regardless of adherence to allocation and adjusting for stratification variables. Trial registration: ISRCTN21528841. Findings 1394 newborns were randomised between November 2014 and November 2016; 693 emollient and 701 control. Adherence in emollient group was 88% (466/532), 82% (427/519) and 74% (375/506) at 3, 6 and 12 months in those with complete data. At 2 years, eczema was present in 139/598 (23%) children in the emollient group and 150/612 (25%) in controls, adjusted relative risk 0·95, 95% CI 0·78 to 1·16, p=0·61 and adjusted risk difference -1·2%, 95% CI -5·9% to 3·6%. Other eczema definitions supported the primary analysis. Mean number of skin infections per child in year 1 was 0·23 (SD 0·68) in the emollient group versus 0·15 (SD 0·46) in controls; adjusted incidence rate ratio 1·55 95% CI 1·15 to 2·09. Interpretation We found no evidence that daily emollient during the first year of life prevents eczema in high-risk children and some evidence to suggest an increased risk of skin infections. Funding National Institute for Health Research Health Technology Assessment (12/67/12) funded the main trial. Supplementary funding for food allergy assessments was from Goldman Sachs Gives and the Sheffield Children’s Hospital Charity.