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

Abstract

Biologic therapies improve outcomes in severe chronic rhinosinusitis with nasal polyps (CRSwNP), but their comparative efficacy remains uncertain. We compared the efficacy and safety of 7 biologic agents (dupilumab, omalizumab, mepolizumab, benralizumab, depemokimab, tezepelumab, and stapokibart) for the treatment of severe CRSwNP. 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. 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. 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.