{'fraction_non_alphanumeric': 0.04028436018957346, 'fraction_numerical': 0.02754739336492891, 'mean_word_length': 4.772649572649573, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Long‐term safety of dupilumab in children

Atopic dermatitis (AD) affects up to 20% of children worldwide, with dramatic impact on quality of life. Dupilumab, a human monoclonal antibody that blocks interleukin (IL)-4 and IL-13, is the first biologic agent approved to treat AD in children aged 6–12 years. In this issue of the BJD, Cork et al. present the 52-week open-label extension (OLE) study of children 6–12 years old with severe AD who received dupilumab in a 16-week phase IIa study. Sixteen children received weekly doses of 2 mg kg, and 17 received 4 mg kg. This contrasts with FDA-approved less frequent dosing. The authors highlight that weekly dosing did not result in increased concentrations at steady state compared with biweekly dosing in other populations, and propose saturable kinetics as a likely reason. Primary endpoints, in addition to dupilumab concentration–time profile, were treatment-emergent adverse events. In the OLE for 2-mgand 4-mg kg groups, adverse effects included, respectively, skin infections (29%, 38%), conjunctivitis (12%, 31%) and injection site reactions (12%, 6%). All cases of conjunctivitis were classified as bacterial or allergic, and resolved with topical therapy. Skin infections are a recognized complication of untreated AD. Notably, in the 16-week randomized trial of dupilumab in this population, children in the placebo group had higher rates of infection than did those receiving dupilumab. In the OLE, the 2-mgvs. the 4-mg kg group had more eczema flares (5% vs. 2%) and bacterial infections (24% vs. 19%), whereas the 4-mg kg group had more viral infections (25% vs. 0%). More data are needed to verify if better eczema control with higher dosing is accompanied by increased viral infections. Secondary endpoints evaluated efficacy, including the Investigator Global Assessment scale (IGA), Eczema Area and Severity Index (EASI), and Children’s Dermatology Life Quality Index. Most patients had continued improvement in efficacy through the study, although 4-mg kg dosing did not result in superior results to 2 mg kg at 1 year. In the 2-mg kg group, a ≥ 75% reduction in EASI (EASI75) was achieved by 59% at 16 weeks and 94% at 52 weeks, with IGA 0–1 in 35% at 16 weeks and 76% at 52 weeks. In the 4-mg kg group, EASI75 was achieved by 73% at 16 weeks and 75% at 52 weeks, with IGA 0–1 in 40% at 16 weeks and 25% at 52 weeks. The small sample size and controlled study environment are important limitations to generalizability. This study did not assess pre-existing risk factors for conjunctivitis. In practice settings, baseline ophthalmology assessment should be considered in children with eyelid eczema or dry eyes when initiating dupilumab, as these were risk factors in studies for ocular side-effects in adults. Most patients do not require discontinuation due to conjunctivitis. Notably, no information is available on optimal therapy duration or effects of treatment interruptions. This is an exciting time for paediatric AD, with many other targeted treatments on the horizon. Data are needed to compare the efficacy of dupilumab with older systemic agents in this population and newer agents as they are introduced. Use of harmonized assessment tools will allow these data to be included in current meta-analyses, along with the anticipated results for ciclosporin and methotrexate from current trials.