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

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. 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. 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). 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.