Mepolizumab and Dupilumab Show No Significant Difference in Reducing Exacerbations in Patients with COPD and an Eosinophilic Phenotype: Matching-Adjusted Indirect Treatment Comparison

Background Mepolizumab and dupilumab are monoclonal antibodies targeting type 2 inflammation that are both approved as add-on maintenance treatment in patients with inadequately controlled chronic obstructive pulmonary disease (COPD) and an eosinophilic phenotype. Research Question What is the comparative efficacy of mepolizumab and dupilumab in reducing the risk of exacerbations and improving health-related quality of life in patients with COPD and an eosinophilic phenotype? Study Design and Methods This study used a robust matching-adjusted indirect comparison (MAIC) approach to compare pooled efficacy data from three Phase III, randomized, placebo-controlled COPD trials of mepolizumab (METREX [NCT02105948], METREO [NCT02105961], and MATINEE [NCT04133909]) with two trials of dupilumab (BOREAS [NCT03930732] and NOTUS [NCT04456673]). An indirect comparison was performed using MAIC, reweighting individual patient data from mepolizumab trials using propensity score-based methods to match the aggregate baseline characteristics of the dupilumab trial populations. To match the more restrictive eligibility criteria of the dupilumab trials, patients from the mepolizumab studies were included in this MAIC if they had blood eosinophil counts ≥300 cells/μL at screening, modified Medical Research Council scale grade ≥2, moderate-to-severe airflow limitation, and chronic bronchitis (CB) (defined by investigator assessment or St George’s Respiratory Questionnaire for COPD [SGRQ-C]). Outcomes included rate/risk of exacerbations and health-related quality of life (SGRQ-C). Results No statistically significant differences were observed in the reduction of the annualized rate of moderate/severe exacerbations (rate ratio [95% confidence interval]: 0.91 [0.60, 1.37] using investigator-assessed CB and 1.13 [0.80, 1.58] using SGRQ-C CB definition). No statistically significant differences were observed in SGRQ-C changes. Interpretation In this MAIC study, there were no statistically significant differences between mepolizumab and dupilumab in the magnitude of effect in reducing moderate/severe exacerbations and improving health-related quality-of-life outcomes.