Dosing Interval Extension of Dupilumab in CRSwNP: Five‐Year Real World Outcomes

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent, often Type 2-mediated inflammatory disease that markedly impairs quality of life. While dupilumab provides rapid improvement, there is limited evidence on long-term outcomes beyond 2 years, and the clinical impact of dosing-interval extension remains unclear. We therefore set out to evaluate long-term real-world outcomes of dupilumab therapy in CRSwNP and assess the effectiveness and safety of dosing-interval extension after achieving disease control. METHODS: This retrospective single-center cohort included 224 adults with CRSwNP (37% with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease) treated with dupilumab for up to 4.5 years with outcomes modeled to 5 years. Longitudinal changes in polyp size, symptom burden, olfaction, asthma control, and Type 2 biomarkers were analyzed using mixed-effects models. Outcomes were then compared between patients who maintained standard 2-week dosing and those who voluntarily extended dosing intervals after achieving stable control. RESULTS: Dupilumab led to significant improvements in polyp burden, olfactory function, and quality of life peaking within 6 months, with sustained benefit through 5 years according to longitudinal modeling. Forty percent of patients extended dosing intervals without loss of efficacy and reported fewer treatment-related adverse events. Overall, 16% experienced side effects, most commonly musculoskeletal complaints, followed by skin reactions and injection site reactions. CONCLUSION: Long-term dupilumab therapy provided durable disease control and excellent safety. Personalized dosing-interval extension maintained efficacy and reduced treatment burden, supporting its potential role in optimizing long-term management of CRSwNP, especially in patients with troublesome side effects.