Comparative Effectiveness of Mepolizumab Versus Dupilumab in Medicare Fee-for-Service Beneficiaries with Asthma: A Real-World Cohort Study

INTRODUCTION: Mepolizumab and dupilumab are biologic therapies used to manage uncontrolled asthma, though direct comparative real-world evidence between these two agents is limited. This study compared asthma-related hospitalizations and asthma exacerbations between mepolizumab and dupilumab among an older and clinically complex population of Medicare fee-for-service (FFS) beneficiaries with asthma. METHODS: Data from Komodo Research Database (01/01/2018-05/31/2025) were used to identify Medicare FFS beneficiaries with asthma and a first claim for mepolizumab or dupilumab on or after January 1, 2019 (index date), as well as a subgroup of patients adherent to the index biologic for ≥ 6 months. Cohorts were balanced using overlap weighting based on a propensity score model. Rates of asthma-related hospitalizations and asthma exacerbations were evaluated while on treatment as the number of events per patient-year (PPY) and compared between weighted cohorts using rate ratios (RRs) with 95% confidence intervals (CIs). Rates of asthma-related hospitalizations were assessed for non-inferiority using a fixed-margin approach. RESULTS: Overall, 1055 and 1218 patients were included in the mepolizumab and dupilumab cohorts, respectively (mean age 70.1 and 67.4 years). Baseline characteristics were well balanced after weighting. Mepolizumab demonstrated non-inferiority to dupilumab for asthma-related hospitalizations within the overall population (RR 0.71, 95% CI 0.46, 1.08; p = 0.113; non-inferiority margin 1.10) and superiority to dupilumab within the adherent subgroup (RR 0.54, 95% CI 0.30, 0.99; p = 0.047). Mepolizumab was also associated with significantly lower rates of asthma exacerbations than dupilumab in the overall population (RR 0.85, 95% CI 0.72, 1.00; p = 0.047) and directionally favorable rates in the adherent subgroup (RR 0.82, 95% CI 0.63, 1.05; p = 0.116). CONCLUSIONS: Among Medicare FFS beneficiaries, mepolizumab demonstrated comparable real-world effectiveness to dupilumab for asthma-related hospitalizations and was associated with significantly lower rates of asthma exacerbations, supporting mepolizumab as an effective treatment option for older, clinically complex patients with asthma.