Optimizing Biologic Treatment Selection in Chronic Rhinosinusitis with Nasal Polyps: A Network Meta-Analysis of Efficacy and Safety Across 22 RCTs

Background/Objectives: Biological therapies have emerged as targeted treatments for chronic rhinosinusitis with nasal polyps (CRSwNP), yet direct comparisons between agents remain limited. This network meta-analysis (NMA) aimed to evaluate and rank the efficacy and safety of biological therapies for CRSwNP in adult patients. Methods: We conducted a systematic review and NMA of randomized controlled trials (RCTs) assessing biological therapies for CRSwNP. A literature search was conducted through July 2025. Eligible RCTs compared approved or investigational biologics with a placebo and reported clinical, functional, or safety outcomes in adults with CRSwNP. The mean differences (MDs) in the least-squares mean change from baseline were used for continuous outcomes, and odds ratios (ORs) were used for binary outcomes. A frequentist random-effects model was used to estimate pooled effects and treatment rankings. SUCRA values and rank probabilities were derived to determine the relative efficacy and safety. Results: A total of 22 RCTs (46 reports; 4068 patients) evaluating eight biologics were included. Dupilumab consistently ranked among the top three agents across most efficacy outcomes, including nasal polyp score (NPS), nasal congestion score (NCS), SNOT-22, UPSIT, and endoscopic scores. CM310 and Tezepelumab also demonstrated strong performance in objective and symptom-based outcomes. For responder outcomes, CM310 was ranked best in minimal clinically important differences across multiple domains. PF-06817024 ranked best in minimizing any adverse events and serious adverse events. The placebo ranked worst across nearly all endpoints. Conclusions: Dupilumab, CM31 0, and Tezepelumab exhibit the most favorable efficacy profiles across multiple CRSwNP domains, while all drugs show a nearly similar safety profile.