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

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 1.71; 95% CI 1.18, 2.48), 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. Chronic obstructive pulmonary disease (COPD) is a long-term lung condition that causes breathing difficulties and frequent flare-ups, also known as exacerbations. In some people with COPD, a type of inflammation known as type 2 inflammation is present. This inflammation is often linked to higher levels of white blood cells called eosinophils. These patients may be more likely to experience exacerbations and worsening symptoms. Two injectable treatments, dupilumab and mepolizumab, have recently been studied in people with COPD who have this type of inflammation (so-called eosinophilic phenotype). Both drugs have shown benefits when added to triple inhaler therapy regimen, but they have not been directly compared in the same clinical trial. This study used a method called an indirect treatment comparison, which uses results from dupilumab and mepolizumab trials to estimate how well these two treatments compare. The results indicate a trend suggesting that dupilumab may offer greater benefit than mepolizumab in reducing the number of moderate or severe COPD exacerbations. People treated with dupilumab also experienced better lung function and were more likely to report fewer breathing symptoms, as well as improved quality of life. Although safety comparisons were not part of the indirect treatment comparison, safety results from dupilumab and mepolizumab trials appeared to be similar. These findings suggest that dupilumab may offer greater overall benefits for people with COPD and type 2 inflammation. However, direct head-to-head trials are necessary to confirm these results and better guide treatment choices.