Efficacy and Safety of Dupilumab in Children With Moderate-to-Severe Asthma: A Systematic Review of Emerging Phase 3 Evidence.

backgroundDupilumab is a human monoclonal antibody targeting the IL-4 receptor. There is a paucity of evidence regarding its efficacy and safety in pediatrics. Pediatric-specific data are limited, and most evidence comes from recent phase 3 trials and post hoc analyses.

objectiveTo summarize the current evidence of the efficacy, safety, and biomarker effects of dupilumab in children with moderate-to-severe asthma, while identifying key gaps in the pediatric evidence base.

methodsThis study is a systematic review following PRISMA guidelines, and aims to assess the efficacy, safety, and biomarker response of dupilumab in pediatric patients with moderate to severe asthma. We evaluated the studies using the Cochrane Risk of Bias Tool 2.0.

resultsSix studies from 2021 to 2024 met the inclusion criteria: three of them are phase 3 randomized controlled trials and the other three post hoc analyses, mostly including children aged 6-11 years with type 2 inflammation, defined by elevated blood eosinophils and/or FeNO. Both allergic and nonallergic asthma phenotypes were represented across studies, with post hoc analyses indicating consistent benefit in each group. Dupilumab decreased the rate of severe exacerbations annually by 59.3% in children with type 2 inflammation. The study populations are mainly children between 6 and 11 years of age with moderate-to-severe asthma, characterized by eosinophilic or allergic phenotypes (type 2 asthma), including those with elevated blood eosinophils and/or FeNO levels. Dupilumab reduced the annual rate of severe exacerbation by ~59%, with greater reductions in children with FeNO ≥50 ppb (69%) or eosinophils ≥300 cells/µL (65%). The lung function showed improvement by 0.15-0.30 L in pre-bronchodilator FEV₁, accompanied by gains in asthma control and quality of life. Biomarker reductions (FeNO, eosinophils, IgE, TARC) were consistent across phenotypes. Adverse event rates were like placebo; eosinophilia and injection site reactions were more common but usually mild.

conclusionThis systematic review provides an early synthesis of emerging pediatric phase 3 evidence on dupilumab. While results suggest substantial benefits in reducing exacerbations, improving lung function, and modulating type 2 biomarkers, the evidence remains limited to short-term studies in a narrow age range. Longer-term follow-up, broader age representation, and real-world data are needed to define the long-term role of dupilumab in pediatric asthma. Prospero Code: CRD42024557750.