Biologics for Children and Adolescents with Asthma: A Systematic Review and Exploratory Indirect Comparative Analysis

Abstract

Background Biologics targeting type 2 inflammation have expanded treatment options for children and adolescents with uncontrolled asthma, but pediatric randomized evidence is limited and direct head-to-head comparisons are unavailable. We reappraised comparative efficacy and safety evidence and the certainty of current indirect estimates. Methods We searched PubMed, Embase, ClinicalTrials.gov, the China National Knowledge Infrastructure, and public trial sources through May 25, 2026, for randomized controlled trials of biologics in children or adolescents with asthma. The primary efficacy outcome was annualized exacerbation rate (AER); safety outcomes were adverse events (AEs) and serious adverse events (SAEs). Between-biologic effects were explored using Bucher adjusted indirect comparisons through placebo as the common comparator. Transitivity was assessed qualitatively, and evidence certainty was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Results Three placebo-controlled pediatric trials evaluating omalizumab, dupilumab, and mepolizumab contributed to the primary analysis. Each biologic reduced AER versus placebo. The adjusted indirect estimate for dupilumab versus mepolizumab was below 1, but this finding was derived from a sparse, clinically heterogeneous evidence structure and was considered hypothesis-generating rather than evidence of superiority. Omalizumab and dupilumab were not associated with a clear increase in overall AEs, whereas mepolizumab had higher broad AE reporting in MUPPITS-2. SAE estimates were imprecise. Certainty was moderate for biologics versus placebo on AER, low for between-biologic comparisons, and low to very low for safety outcomes. Conclusion Randomized pediatric evidence supports biologics for reducing exacerbation burden versus placebo. Current adjusted indirect estimates do not establish a biologic hierarchy. Phenotype-stratified head-to-head pediatric trials remain necessary.