Safety and Tolerability of Biologic Therapies for Chronic Rhinosinusitis with Nasal Polyps: A Systematic Review of Randomized Controlled Trials

Biologic therapies targeting type 2 inflammation are increasingly used for severe Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Because individual trials are generally powered for efficacy rather than uncommon harms, this review aimed to synthesize randomized evidence on the safety and tolerability of biologic therapies in adults with CRSwNP.

This systematic review followed the PRISMA 2020 guidelines. Eligible studies were parallel-group randomized trials in adults with CRSwNP that compared a biologic with placebo or standard care and reported extractable safety outcomes. Trial families were reconciled to prevent double counting. Risk of bias was assessed using Cochrane RoB 2. Risk Ratios (RRs) were synthesized with Paule-Mandel random-effects models and modified Hartung-Knapp confidence intervals. Certainty was assessed using GRADE.

Twenty unique randomized controlled trials reported in 17 primary publications comprised 3,598 randomized participants and eight biologic agents. Thirteen trials were at low overall risk of bias, and seven raised some concerns; none was high risk. Twelve independent safety-analysis units involving 2,962 participants showed little or no difference in any adverse event/treatment-emergent adverse event (RR 1.00, 95% CI 0.94-1.05; I²=18%; high-certainty evidence). Nine units involving 2,329 participants showed no statistically significant difference in serious adverse events (RR 0.75, 95% CI 0.48-1.19; I²=0%; moderate-certainty evidence). Adverse-event-related discontinuation was numerically less frequent with biologics across seven units involving 2,569 participants, but remained imprecise (RR 0.55, 95% CI 0.28-1.08; I²=0%; moderate-certainty evidence).

The pooled randomized evidence indicates no clinically significant generalized increase in short- to medium-term adverse-event burden with biologic therapy. Estimates for serious adverse events and adverse-event-related discontinuation were less precise, so uncommon, delayed, and agent-specific harms remain important targets for longer-term surveillance.

Biologic therapy for CRSwNP results in little or no difference in overall short- to medium-term adverse-event risk compared with placebo or standard care. Serious adverse events were not demonstrably increased, while a possible reduction in adverse-event-related discontinuation remains uncertain. Randomized trials cannot exclude uncommon, delayed, or agent-specific harms.