Abstract Rationale Up to 40% of patients with chronic obstructive pulmonary disease (COPD) exhibit type 2 inflammation, driven by eosinophilic pathways mediated in part by interleukin (IL)-4, IL-5, and IL-13. Dupilumab and mepolizumab are monoclonal antibodies targeting IL-4/IL-13 receptors and IL-5, respectively. Both are approved maintenance therapies for COPD with type 2 inflammation and reduce moderate-to-severe COPD exacerbations versus placebo. However, comparative efficacy between these therapies remains unclear. Methods We conducted a retrospective, propensity score-matched analysis using the TriNetX database, which provides de-identified electronic medical records from over 100 healthcare institutions. Adults with COPD who initiated dupilumab or mepolizumab within 6 months of diagnosis, and using background combined inhaled corticosteroid, long-acting beta-agonist, and long-acting muscarinic antagonist therapy, were included. Dupilumab users were identified between October 1, 2024, and October 1, 2025, and mepolizumab users between January 1, 2023, and October 1, 2025 (FDA-approved May 22, 2025), due to limited post-approval mepolizumab users. Propensity score matching (1:1) balanced baseline characteristics, resulting in 145 patients in each cohort from 728 dupilumab and 154 mepolizumab-eligible patients. Cox proportional hazard models were used to assess the association of dupilumab and mepolizumab use with COPD exacerbations, emergency department (ED) visits, and inpatient admissions. All outcomes were defined as events occurring between 1 day and 1 year after the index date. Results ED visits were numerically higher in the mepolizumab group compared to dupilumab (19.3% vs. 11.7%), but this difference was not statistically significant (hazard ratio HR 0.699, 95% confidence interval CI 0.376-1.298, p = 0.254). Rates of inpatient admissions (HR 1.384, 95% CI 0.731-2.622, p = 0.319) and COPD exacerbations (HR 1.344, 95% CI 0.821-2.199, p = 0.238) were similar between groups (Table 1). Outcomes for all-cause mortality and ICU admissions were too infrequent (10 events per group) for a reliable statistical comparison. Conclusion Our study found no significant differences in ED visits, inpatient admissions, or COPD exacerbations, though mepolizumab showed a non-significant trend toward increased ED visits. Recent randomized controlled trials (BOREAS, NOTUS, MATINEE) noted that IL-4/IL-13 inhibition provides broader and consistent improvements in lung function and symptoms when compared to IL-5 inhibition despite both reducing annualized rates of COPD exacerbations. Post-treatment spirometry, quality of life and symptom scores were not assessed in our study, therefore limiting comparison between these drug classes. This abstract is funded by: None
Lee et al. (Fri,) studied this question.