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

In brief

Biologic therapies lower asthma exacerbation rates in children compared with placebo

Three pediatric trials of omalizumab, dupilumab and mepolizumab each showed fewer asthma attacks than placebo, with moderate certainty for this benefit. Safety was similar for omalizumab and dupilumab, while mepolizumab reported more overall adverse events and serious events were uncertain. Indirect comparisons were low-certainty, so head-to-head trials are still needed.

Journal
Journal of asthma and allergy (Q1)
Published
10 September 2026
Study design
Systematic review / meta-analysis of RCTs
Evidence level
Level 1, High (CEBM 1a)
Authors
Mengwei Wu, Haoyuan Li, He Geng, Peize Liu, Chao Wang, Ling Zhou, et al.
PMID
42741706
DOI
10.2147/JAA.S629339

Why clinicians should know about it

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.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.