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

Document Type

Conference Proceeding

Publication Date

5-15-2026

Publication Title

Am J Respir Crit Care Med

Keywords

General & Internal Medicine, Respiratory System

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.

Volume

212

First Page

2

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