Efficacy and Predictors of Response to Biologic Therapy and Endoscopic Sinus Surgery in Patients With Nasal Polyps: A Systematic Review.

BACKGROUND: Biologics and endoscopic sinus surgery (ESS) treat refractory chronic rhinosinusitis with nasal polyposis (CRSwNP), but direct comparisons are lacking. We synthesized efficacy and subgroup data across randomized controlled trials (RCTs) of biologics and ESS. METHODS: PubMed was searched through December 2025 for RCTs and subgroup analyses of biologics or ESS for adult CRSwNP. Included were ten Phase-3 placebo-controlled biologic RCTs, two pragmatic ESS trials, and one head-to-head biologic trial. 22-Item Sino-Nasal Outcome Test (SNOT-22) and nasal polyp score (NPS) effect sizes and subgroup interactions were extracted. RESULTS: A total of 13 trials (n = 3775) from 21 publications were included. By indirect comparison, tezepelumab and dupilumab produced the largest improvements (tezepelumab: SNOT-22: -27.4; NPS: -2.1; dupilumab: SNOT-22: -17 to -21; NPS: -1.7 to -2.1), while mepolizumab and omalizumab showed intermediate effects (SNOT-22: -10.6 to -16.5); benralizumab improved NPS but not SNOT-22, and depemokimab showed improvement below clinically discernible differences. ESS effects varied by trial and follow-up (SNOT-22: -21.9 at 6 months in MACRO vs. -4.9 at 12 months in PolypESS). Predictors of improvement differed across therapies (blood eosinophil count, NSAID-exacerbated respiratory disease, and prior ESS for dupilumab; asthma for benralizumab; baseline severity for ESS), while tezepelumab and omalizumab showed consistent efficacy without effect modification. CONCLUSIONS: ESS and biologics provide clinically meaningful benefit. Among biologics, dupilumab and tezepelumab demonstrated the largest effect sizes, though cross-trial differences in baseline severity, follow-up, and comparators limit indirect comparisons. Head-to-head trials and standardized subgroup analyses are needed to guide treatment selection.