Biologics for Chronic Rhinosinusitis with Nasal Polyps: Dupilumab Versus Mepolizumab

Abstract

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is driven by type 2 inflammation. Biologics targeting IL-4/IL-13 (dupilumab) or IL-5 (mepolizumab) are effective but head-to-head comparisons are lacking. Methods: Systematic review of 6 RCTs (n=1,892) and 3 real-world cohorts (n=412). Inclusion: moderate-to-severe CRSwNP despite prior surgery or systemic steroids. Outcomes at 24 weeks: nasal polyp score (NPS, 0–8), Sino-Nasal Outcome Test (SNOT-22), sense of smell (UPSIT), need for surgery. Results: Dupilumab reduced NPS by –3.1 points (vs placebo –0.4) and SNOT-22 by –24 points (vs –6). Mepolizumab reduced NPS by –2.0 and SNOT-22 by –18. Indirect comparison favored dupilumab (p=0.02 for NPS). Dupilumab also improved smell significantly more (UPSIT +8 vs +4). Adverse events: injection site reactions (dupilumab 12%, mepolizumab 8%). Discussion: Broader cytokine blockade (IL-4/IL-13) may be more effective than isolated IL-5 inhibition for polyp reduction and smell restoration. Conclusion: Dupilumab appears more effective than mepolizumab for CRSwNP, but direct RCTs are needed.