Indirect Treatment Comparison of Tezepelumab Versus Other Biologics in Severe Chronic Rhinosinusitis with Nasal Polyps: A Systematic Literature Review and Network Meta-analysis

INTRODUCTION: This study compared the efficacy of tezepelumab with other approved biologics and endoscopic sinus surgery (ESS) using indirect treatment comparisons (ITCs) in adults with severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Randomized controlled trials (RCTs) identified via a systematic literature review (SLR) were synthesized in a network meta-analysis (NMA). Outcomes included change from baseline in nasal polyp score (NPS), nasal congestion/obstruction score (NCS/NOS), difficulty with sense of smell (DSS), Sino-Nasal Outcome Test-22 (SNOT-22) score, Lund Mackay score (LMS), time to nasal polyposis (NP) surgery decision, proportions requiring NP surgery or systemic corticosteroids (SCS), time to SCS use, and the University of Pennsylvania Smell Identification Test (UPSIT). Mean differences, hazard ratios, and odds ratios with 95% credible intervals were estimated for available treatments at 52 weeks. Not all endpoints were reported across trials; comparisons were conducted only where both treatments reported the outcome. RESULTS: At 52 weeks, tezepelumab showed comparable efficacy to dupilumab across all evaluated endpoints, apart from the proportion of patients requiring surgery, where tezepelumab was associated with a lower surgery rate than dupilumab. Tezepelumab consistently outperformed mepolizumab, depemokimab, and placebo. In analyses of < 30-week endpoints, tezepelumab outperformed omalizumab for all outcomes except SNOT-22, where no difference was observed. Sensitivity analyses including ESS showed benefits for tezepelumab across endpoints except for NPS, for which ESS ranked highest. CONCLUSION: Tezepelumab achieved similar efficacy to dupilumab across all evaluated endpoints with the exception of the proportion of patients requiring surgery, where tezepelumab demonstrated a numerically greater reduction compared with dupilumab. Results consistently favoured tezepelumab and dupilumab over depemokimab, mepolizumab, and omalizumab.