Comparative efficacy of biologic agents for severe chronic rhinosinusitis with nasal polyps: Systematic review and network meta-analysis

Background: Biologic therapies improve outcomes in severe chronic rhinosinusitis with nasal polyps (CRSwNP), but their comparative efficacy remains uncertain. Objective: We compared the efficacy and safety of 7 biologic agents (dupilumab, omalizumab, mepolizumab, benralizumab, depemokimab, tezepelumab, and stapokibart) for the treatment of severe CRSwNP. Methods: We systematically reviewed randomized trials in PubMed and EMBASE evaluating biologic agents for severe CRSwNP. Primary outcomes were changes in nasal polyp score (NPS) and nasal congestion score (NCS) at 20-24 and 48-56 weeks. Secondary outcomes included changes in loss-of-smell test, 22-item Sinonasal Outcome Test, University of Pennsylvania Smell Identification Test, Lund-Mackay scores, need for nasal polyp surgery or systemic corticosteroids, and safety. We used mean differences and odds ratios with 95% confidence intervals for analysis. Results: Fifteen randomized trials involving 3,642 patients were included. At 20-24 weeks, dupilumab and stapokibart produced greater reductions in NPS and NCS compared to depemokimab, omalizumab, and benralizumab, with no significant differences between dupilumab and stapokibart for NPS (mean difference [95% confidence interval]: 0.29 [−0.97, 0.40]) and NCS (0.19 [−0.03, 0.42]). At 48-56 weeks, dupilumab and tezepelumab produced greater reductions in NPS and NCS than depemokimab, mepolizumab, or benralizumab; no significant differences were observed between dupilumab and tezepelumab for NPS (0.32 [−0.17, 0.81]) and NCS (0.06 [−0.19, 0.31]). Dupilumab, tezepelumab (at 48-56 weeks only), and stapokibart (at 20-24 weeks only) showed superior outcomes for secondary end points against other tested biologics. Safety profiles were comparable across agents. Conclusion: Dupilumab, tezepelumab, and stapokibart were associated with greater clinical benefit than other biologics in severe CRSwNP. Indirect comparisons did not demonstrate superiority of stapokibart (at 20-24 weeks) or tezepelumab (at 48-56 weeks) over dupilumab, highlighting the need for direct comparative trials. © 2026 American Academy of Allergy, Asthma & Immunology