Efficacy, Safety, Quality of Life, and Adherence of Dupilumab in Pediatric Atopic Dermatitis: A Systematic Review.

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease that disproportionately affects children, often causing significant physical, psychological, and social burdens. While biologic therapies have transformed AD management in adults, pediatric-specific evidence remains limited. Dupilumab, an interleukin (IL)-4 receptor α antagonist that inhibits IL-4 and IL-13 signaling, is currently the only US Food and Drug Administration (FDA)-approved biologic for pediatric AD.

OBJECTIVE: To systematically review the efficacy, safety, quality of life, and adherence of dupilumab in children (0-12 years) with moderate-to-severe AD.

METHODS: This review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. PubMed, Embase, and Cochrane Library were searched from inception to August 10, 2024, for studies involving biologic use in pediatric AD. Eligible designs included randomized controlled trials (RCTs), open-label extensions, observational studies, case series, and case reports reporting validated efficacy, safety, quality of life, or adherence outcomes. Risk of bias was assessed using the Mixed Methods Appraisal Tool (MMAT). Results were synthesized narratively, stratified by study design and age group; meta-analysis was not performed due to heterogeneity in study designs, outcome measures, and follow-up durations.

RESULTS: Of 1576 records screened, 20 studies (n= around 1200; age range: 5 months to 12 years) met inclusion criteria. Across study designs, dupilumab produced rapid and sustained improvements in disease severity, with mean Eczema Area and Severity Index (EASI) reductions of 62-92% and high EASI-75 response rates (53-94%) within 16-52 weeks. Quality of life gains were substantial, including large reductions in Children's Dermatology Life Quality Index scores (up to ~89%) and marked sleep improvement. Adverse events were generally mild; conjunctivitis (0-20%) was the most common, with rare herpesvirus infections and injection-site reactions. Laboratory abnormalities including eosinophilia and alkaline phosphatase (ALP) elevation were typically asymptomatic and transient. Adherence was high (≥90% in most cohorts), with low discontinuation rates. Data were synthesized across two developmental age groups where possible: children aged 6 months to 5 years and children aged 6 to 11 years. Some studies reported numerically higher or faster responses in younger children (<6 years), although findings were inconsistent across cohorts and limited by differences in disease duration, dosing, and sample size. The predominantly observational and uncontrolled study designs, heterogeneity in outcome measures and follow-up durations, and small sample sizes in several cohorts limit the certainty of the evidence.

CONCLUSIONS: Dupilumab demonstrates robust efficacy, durable benefits, and a favorable safety profile in pediatric AD, with meaningful improvements in quality of life and adherence. Evidence supports its consideration as a systemic option for moderate-to-severe disease inadequately controlled by topical therapy. Future research should address long-term outcomes, comparative effectiveness versus conventional immunosuppressants, age-stratified response patterns and their confounders, and cost effectiveness in diverse healthcare settings.