Individualising biologic therapy for paediatric severe asthma: A comparative review of all five approved agents, real-world evidence, and a biomarker-guided clinical decision algorithm.

Severe asthma affects 5-10% of children with asthma yet accounts for disproportionate morbidity and healthcare utilisation. The recent expansion of biologic therapies-targeting IgE, IL-5, IL-4/13, TSLP, and IL-5 receptor α-has transformed management but introduced complexity into clinical decision-making. This review provides a comprehensive, comparative analysis of currently approved biologic agents for paediatric severe asthma, with emphasis on efficacy, safety, biomarker-guided selection, and practical implementation. We searched PubMed/MEDLINE (2015-2026) for randomised controlled trials, systematic reviews, and observational studies evaluating biologic therapies in children and adolescents with severe asthma, using a narrative synthesis approach.Five biologic agents are currently approved for paediatric severe asthma. Omalizumab (anti-IgE) reduces exacerbations by 38-50% in allergic asthma (≥6 years). Mepolizumab (anti-IL-5) reduces exacerbations by 27% (rate ratio 0.73; 95% CI 0.56-0.96) in eosinophilic asthma in children and adolescents aged 6-17 years (MUPPITS-2). Dupilumab (anti-IL-4Rα) reduces exacerbations by 59% and improves lung function in children 6-11 years (VOYAGE). Tezepelumab (anti-TSLP) reduces exacerbations by 56% and is the first agent effective in T2-low phenotypes (≥12 years; NAVIGATOR). Benralizumab (anti-IL-5Rα) induces near-complete eosinophil depletion with extended every-8-week maintenance dosing; FDA approval was extended to children ≥6 years in April 2024 based on the TATE trial (SIROCCO/CALIMA/BORA/TATE). Safety profiles are generally favourable; dupilumab-associated conjunctivitis and omalizumab-related anaphylaxis require specific monitoring protocols.Biologic therapies have ushered paediatric severe asthma into the precision medicine era. Dupilumab and tezepelumab demonstrate robust efficacy across multiple phenotypes, while biomarker assessment enables rational, individualised selection.