B101-08 Pooled Efficacy of Mepolizumab in Eosinophilic COPD: Meta-Analysis of the Metrex, Metreo, and Matinee Randomized Trials

Abstract Rationale Eosinophilic airway inflammation represents a mechanistically distinct endotype of chronic obstructive pulmonary disease (COPD), characterized by recurrent exacerbations that persist despite optimal triple inhaled therapy. Mepolizumab, a monoclonal antibody targeting interleukin-5, reduces eosinophil survival and migration, potentially mitigating inflammation-driven disease activity. Previous trials such as METREX and METREO suggested clinical benefit but were underpowered to confirm consistent efficacy. With the recent publication of the large phase 3 MATINEE trial, a unified synthesis of all available data became essential to establish the reproducibility and magnitude of mepolizumab’s effect in eosinophilic COPD. We therefore conducted an integrated meta-analysis of the METREX, METREO, and MATINEE randomized controlled trials to clarify the pooled treatment benefit at the approved clinical dose of 100 mg subcutaneously every four weeks. Methods All three studies were multicenter, double-blind, placebo-controlled trials enrolling patients with blood eosinophil counts of at least 150 cells/μL at screening or 300 cells/μL historically. The primary endpoint across trials was the annualized rate of moderate-to-severe exacerbations, while time-to-first exacerbation served as the secondary endpoint. Data were combined using inverse-variance fixed-effect modeling, and heterogeneity was quantified by the I² statistic. Results A total of 2,592 participants were analyzed (1,302 receiving mepolizumab and 1,290 receiving placebo). Mepolizumab consistently reduced exacerbation frequency: METREX rate ratio (RR) 0.82 (95% CI 0.68–0.98), METREO RR 0.80 (0.65–0.98), and MATINEE RR 0.79 (0.66–0.94). The pooled RR was 0.80 (0.72–0.89) with I² = 0%, demonstrating homogeneity of effect and a 20% overall reduction in annualized exacerbation rate. Time-to-first exacerbation also favored mepolizumab with a pooled hazard ratio of 0.82 (0.71–0.94). Conclusion Mepolizumab 100 mg every four weeks produces a consistent and clinically meaningful reduction in moderate-to-severe exacerbations among patients with eosinophilic COPD. The reproducible benefit across METREX, METREO, and MATINEE, along with minimal heterogeneity, confirms the reliability of IL-5 blockade in this phenotype. These findings strengthen the role of blood eosinophils as a precision biomarker and support biologic therapy as an evidence-based strategy to reduce exacerbation burden.By integrating all phase 3 trials at the approved dose, this meta-analysis provides the first comprehensive post-MATINEE synthesis of mepolizumab efficacy in eosinophilic COPD. Focusing on a unified population and dosing regimen eliminates prior heterogeneity and clarifies the therapeutic signal. These results reinforce a shift toward endotype-driven COPD management, where biologic selection is guided by inflammation profiles rather than airflow severity alone. This abstract is funded by: None