Special Issue: Update on Biologic Therapy in Pediatric Allergy

Issue 4 - 2025

Biologic Therapies Targeting Type-2 Inflammation in Pediatric Chronic Rhinosinusitis: Evidence, Extrapolation From Adults, and a Pediatric Research Agenda

Authors

Alessandra Gori , Bianca Cinicola , Giorgio Colletti , Fabrizio Leone , Elia Pignataro , Caterina Anania , Anna Maria Zicari

Key words: Biologic therapy, Pediatric chronic rhinosinsitis, nasal polyps, type 2 inflammation, dupilumab, mepolizumab, benralizumab, omalizumab, tezepelumab, biomarker, research agenda
DOI: 10.53151/2531-3916/2025-1774
Publication Date: 2026-01-23

Abstract

Pediatric chronic rhinosinusitis (CRS), particularly when complicated by nasal polyps (CRSwNP), spans a spectrum of age-dependent endotypes that challenge one-size-fits-all management. Emerging evidence – integrating pathology, multi-omic profiling, and real-world cohorts – indicates that younger children commonly exhibit non-type-2 (non-T2) inflammation driven by adenoidal disease and biofilm ecology, whereas adolescents increasingly manifest T2-high signatures that mirror adult CRSwNP. Within this context, biologic therapies targeting T2 pathways (anti-IL-4Rα, anti-IL-5/IL-5Rα, anti-IgE, anti-TSLP) have demonstrated multidomain benefits in adults and growing pediatric applicability, improving nasal polyp burden, congestion, olfaction, and steroid/surgery use when standard care is insufficient. Safety profiles across pediatric experience in related T2 diseases are generally favorable, with predictable and manageable adverse events; nonetheless, child-specific long-term data remain limited. This review synthesizes the pathophysiology and endotypes in childhood and adolescence, maps biomarker-guided selection, and summarizes evolving regulatory landscapes. Persistent gaps include the scarcity of randomized pediatric trials, incomplete validation of biomarkers and response criteria for children, and the need for cost-effectiveness analyses that reflect school participation and caregiver burden. Overall, biologics represent a meaningful advance for T2-high adolescent CRSwNP, enabling targeted, generally safe, steroid- and surgery-sparing strategies, while underscoring the imperative for dedicated pediatric trials, standardized endpoints, and robust pharmacovigilance to realize their full potential in comprehensive care.

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Authors

Alessandra Gori - Department of Mother-Child and Urological Science, Sapienza University of Rome, Italy

Bianca Cinicola - Department of Mother-Child and Urological Science, Sapienza University of Rome

Giorgio Colletti - Department of Mother-Child and Urological Science, Sapienza University of Rome, Italy

Fabrizio Leone - Department of Mother-Child and Urological Science, Sapienza University of Rome, Italy

Elia Pignataro - Department of Mother-Child and Urological Science, Sapienza University of Rome, Italy

Caterina Anania - Department of Mother-Child and Urological Science, Sapienza University of Rome, Italy

Anna Maria Zicari - Department of Mother-Child and Urological Science, Sapienza University of Rome, Italy

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Gori, A., Cinicola, B., Colletti, G., Leone, F., Pignataro, E., Anania, C., & Zicari, A. M. (2026). Biologic Therapies Targeting Type-2 Inflammation in Pediatric Chronic Rhinosinusitis: Evidence, Extrapolation From Adults, and a Pediatric Research Agenda. Italian Journal of Pediatric Allergy and Immunology, 39(4). https://doi.org/10.53151/2531-3916/2025-1774
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