Treatment Persistence and Factors Associated With Discontinuation in Real-World Biologic Therapy for Chronic Rhinosinusitis With Nasal Polyps.

Background: Biologic therapies are effective for severe, uncontrolled CRSwNP, yet real-world data on treatment persistence remain limited. Methods: This retrospective single-center study included 95 adults with CRSwNP who initiated dupilumab (88.4%), mepolizumab, or omalizumab between 2021 and 2025. The primary outcome was persistence with the index biologic therapy. Discontinuation was a permanent cessation, switching, or a ≥ 90-day dosing gap. Switching ended index-biologic persistence but not biologic therapy overall. Response was graded with European Position Paper on Rhinosinusitis and Nasal Polyps/European Forum for Research and Education in Allergy and Airway Diseases (EPOS/EUFOREA) criteria. Kaplan-Meier and Cox analyses were performed. Results: Twenty-one patients (22.1%) discontinued their index biologic over a median follow-up of 18 months. Eight switched agents, so 13 (13.7%) stopped biologic therapy altogether. Index-biologic persistence was 82.3% (95% CI: 71.9%-89.2%) at 12 months and 71.7% (95% CI: 58.2%-81.5%) at 30 months. Among discontinuers, the median observed time to discontinuation was 9.4 months. Adverse events were the leading cause (57.1%), most commonly arthralgia and ocular symptoms. Early discontinuation was driven predominantly by adverse events, whereas adverse events and insufficient efficacy contributed equally later. In exploratory univariable Cox analyses, adverse events during therapy (HR = 4.32, 95% CI: 1.73-10.79) and a general history of allergy (HR = 3.07, 95% CI: 1.24-7.58) were most strongly associated with discontinuation, as were female sex, diabetes mellitus, and lower EPOS/EUFOREA response scores. Conclusion: In this real-world cohort, discontinuation of the index biologic was driven mainly by adverse events and insufficient response. Early follow-up focused on tolerability and later review on disease control may be warranted.