The Use of Biomarkers to Justify the Choice of the Proper Biologic Agent for the Treatment of Chronic Rhinosinusitis with Nasal Polyps: A Systematic Review

Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous type 2 inflammatory disease for which biologic therapies have expanded treatment options; however, biomarkers capable of guiding biologic selection remain poorly defined. This systematic review aimed to evaluate the available evidence regarding predictive and prognostic biomarkers associated with currently available biologic agents for CRSwNP (omalizumab, dupilumab, mepolizumab, benralizumab, reslizumab, and tezepelumab). Materials and Methods: A systematic search of PubMed/MEDLINE, Embase, Google Scholar, and the Cochrane Library identified studies published between January 2006 and September 2025. Results: Twenty-five eligible studies, including 12 randomized controlled trials, 12 systematic reviews/meta-analyses, and one indirect treatment comparison study, were analyzed. Multiple biomarkers, including blood eosinophils, total IgE, periostin, eotaxins, eosinophil cationic protein, IL-5, TARC, PARC, and urinary leukotriene E4, were evaluated across biologics targeting IgE, IL-4/IL-13, and IL-5 pathways. Conclusions: Although several biomarkers reflected the modulation of type 2 inflammation and disease activity, no validated biomarker has reliably predicted the superiority of one biologic over another. Nasal IL-5 showed potential for predicting the response to anti-IL-5 therapy but requires further validation. Current evidence supports biomarker use primarily for confirming type 2 inflammation rather than guiding biologic selection. Prospective biomarker-driven and head-to-head comparative studies are needed to enable precision medicine approaches in CRSwNP.