Dupilumab Beyond the Airway: Decreased Morbidity in a Real‐World Analysis

BACKGROUND: Post hoc analyses of clinical trials have characterized dupilumab's adverse effects, yet the real-world impact in chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma is not well described. This study aims to characterize the risks of lymphoma, cardiovascular events, eosinophilia, joint pain, inflammatory arthritis, and sleep apnea in dupilumab-treated CRSwNP and/or asthma patients compared to those not taking dupilumab, and to other biologics. METHODS: This retrospective cohort study used TriNetX, a de-identified database containing over 100 million patient records. Demographics and adverse effects associated with immunotherapy use were collected. RESULTS: We identified 21,249 dupilumab-treated CRSwNP and/or asthma patients. After matching for demographics, comorbid conditions, and medication use, dupilumab was associated with a lower risk of acute myocardial infarction (RR 0.538, 95% CI 0.435-0.665), pulmonary embolism (RR 0.639, 95% CI 0.500-0.817), cerebral infarction (RR 0.716, 95% CI 0.580-0.884), venous thrombosis (RR 0.625, 95% CI 0.511-0.763), cardiovascular disease (RR 0.733, 95% CI 0.678-0.791), and sleep apnea (RR 0.891, 95% CI 0.818-0.970), with a higher risk of eosinophilia (RR 3.157, 95% CI 2.606-3.826), versus no biologic. Dupilumab was associated with a similar risk of lymphoma and musculoskeletal outcomes. Compared to omalizumab and mepolizumab, dupilumab showed a more favorable musculoskeletal and cardiovascular profile, while it demonstrated a largely similar profile to tezepelumab. CONCLUSIONS: Despite eosinophilia, dupilumab was associated with decreased risk of major cardiovascular, thromboembolic, and sleep apnea outcomes in CRSwNP and asthma. These findings suggest dupilumab may confer protection against adverse outcomes beyond respiratory symptom control.