Dupilumab Versus Mepolizumab for COPD: Evaluating Efficacy Outcomes Using Placebo-Adjusted Indirect Treatment...

Up to 40% of patients with chronic obstructive pulmonary disease (COPD) exhibit elevated blood eosinophils, reflective of type 2 inflammation. Dupilumab and mepolizumab versus standard of care have demonstrated moderate-to-severe exacerbation reductions of 30-34% and 15-18%, respectively, over 52 weeks. This study compared their relative efficacy using indirect treatment comparison (ITC).

A Bucher ITC was performed on 52-week phase 3 trials of dupilumab (BOREAS/NOTUS) and mepolizumab (MATINEE/METREX/METREO). The primary ITC endpoint was annualized moderate-to-severe exacerbation rates in patients from BOREAS + NOTUS versus MATINEE + METREX (modified intention-to-treat high stratum cohort, representing an eosinophilic phenotype); sensitivity analyses were performed using different combinations of mepolizumab data including MATINEE + METREX + METREO (100-mg arm). Other 52-week endpoints included mean difference in pre-bronchodilator forced expiratory volume in 1 s (FEV₁), proportion of St. George's Respiratory Questionnaire (SGRQ) improvement ≥ 4 points, proportion of Evaluating Respiratory Symptoms in COPD (E-RS:COPD) improvement ≥ 2 points, and annualized severe exacerbation rate. Rate ratios (RRs)/odds ratios (ORs) with 95% confidence intervals (CIs) are reported.

The primary ITC resulted in an RR of 0.82 (95% CI 0.66, 1.01), showing a numerical advantage for dupilumab versus mepolizumab in reducing moderate-to-severe exacerbation. Sensitivity analyses confirmed findings from the primary ITC (BOREAS + NOTUS vs. MATINEE + METREX + METREO: RR 0.83 [95% CI 0.68, 1.01]). Dupilumab demonstrated significantly greater FEV₁ improvement (mean difference 83.4 mL [95% CI 36.1, 130.7]) and proportion of E-RS:COPD improvement ≥ 2 points (OR 1.76 [95%CI 1.20, 2.54]), with a numerical difference favoring dupilumab for the proportion of SGRQ improvement ≥ 4 points (OR 1.16; [95% CI 0.86, 1.56]) and for annualized severe exacerbation rate (RR 0.61 [95% CI 0.33, 1.13]) versus mepolizumab.

This ITC suggests potential clinical benefits of dupilumab over mepolizumab in reducing exacerbations and improving lung function, respiratory symptoms, and quality of life in patients with COPD and type 2 inflammation. Direct head-to-head trials are necessary to confirm these results and better guide treatment choices.