Prospective Real‐World Outcomes of Endoscopic Sinus Surgery and Dupilumab in Severe Chronic Rhinosinusitis With Nasal Polyps

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease treated with endoscopic sinus surgery (ESS) or targeted biologic therapy such as dupilumab. Prospective real-world data guiding treatment decisions remain limited. MATERIALS AND METHODS: We conducted a single-center, prospective, real-world observational cohort study of adults with severe CRSwNP treated with ESS or dupilumab following structured shared decision-making. All patients met EPOS diagnostic criteria and were followed for 12 months. Standardized assessments were performed at baseline and every 3 months, including disease-specific quality of life (SNOT-22), olfaction (UPSIT-40), nasal congestion score (NCS), and endoscopic nasal polyp score (NPS). CRS exacerbations were prospectively monitored using biweekly symptom surveys, with endoscopic culture obtained during exacerbations with mucopurulence. Longitudinal outcomes were analyzed using mixed-effects models, and bacterial exacerbation incidence was evaluated using regression and survival analyses. RESULTS: Fifty adults completed 12-month follow-up (dupilumab, n = 20; ESS, n = 30). Both treatments resulted in significant improvements across patient-reported and objective outcomes, exceeding minimal clinically important differences. ESS was associated with more rapid early improvement, whereas dupilumab demonstrated more durable improvement in symptoms, olfaction, and nasal congestion. CRS exacerbations and culture-confirmed bacterial infections occurred less frequently in dupilumab-treated patients, with lower cumulative bacterial burden and longer infection-free survival. Staphylococcus aureus was the most common pathogen and more frequent among ESS-treated patients. Bacterial infection was associated with persistently higher symptom burden and worse longitudinal outcomes. CONCLUSIONS: ESS and dupilumab both provide meaningful benefit in severe CRSwNP, with distinct temporal response patterns. Reduced exacerbations and bacterial infections-particularly S. aureus-were associated with more favorable disease trajectories, underscoring the importance of infection control in individualized treatment selection.