A34-11 Mepolizumab Reduces the Burden of Chronic Obstructive Pulmonary Disease Exacerbations in a Wide Spectrum of Patients: Pooled Results From Phase III Randomized Controlled Trials

Abstract Rationale Patients with chronic obstructive pulmonary disease (COPD) and an eosinophilic phenotype, characterized by raised blood eosinophil counts (BEC), experience frequent and severe exacerbations, leading to significant disease burden. Mepolizumab is a humanized monoclonal antibody specifically targeting interleukin-5, approved as an add-on to inhaled triple therapy for the treatment of COPD with an eosinophilic phenotype. Methods Integrated analysis of three randomized, controlled, multicenter, double-blind, Phase III trials: METREX (GSK ID: 117106/ClinicalTrials.gov identifier: NCT02105948), METREO (117113/NCT02105961), and MATINEE (208657/NCT04133909). Patients with COPD (≥1 year diagnosis) receiving inhaled triple therapy were administered mepolizumab 100 mg subcutaneously, or placebo, from 52 (METREX/METREO) up to 104 (MATINEE) weeks. Patients were aged ≥40 years, with a history of exacerbations and airflow obstruction levels of Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 2-4, without a current diagnosis of asthma. Patients were enrolled regardless of presence/absence of symptoms of chronic bronchitis and/or emphysema and modified Medical Research Council dyspnea score. METREX enrolled patients regardless of BEC; METREO with BEC ≥150 cells/µL at screening (or ≥ 300 cells/µL in the previous year); MATINEE with BEC ≥300 cells/µL at screening (and ≥150 cells/µL in the previous year). We report the rate of exacerbations requiring emergency department (ED) visit and/or hospitalization and severe exacerbations (i.e., resulting in ≥ 24hour hospitalization or death), alongside time to first event; in patients with BEC ≥150 cells/µL at screening and/or ≥300 cells/µL in the previous year. Results Of the 2089 patients (1043 mepolizumab/1046 placebo) enrolled in all studies, 1713 (857/856) had BEC ≥150 cells/µL at screening and/or ≥300 cells/µL in the previous year. The annualized rate of exacerbations requiring ED visit and/or hospitalization significantly reduced by 23% with mepolizumab versus placebo (rate ratio [95% confidence interval (CI)]: 0.77 [0.60, 0.99]; P = 0.044); alongside a significant 22% reduction of the hazard of reaching a first such exacerbation at any point up to Week 104 (hazard ratio [95% CI]: 0.78 [0.62, 0.97]; P = 0.029; Figure). The rate of severe exacerbations trended towards a 19% reduction with mepolizumab versus placebo (rate ratio [95% CI]: 0.81 [0.61, 1.06]; P = 0.124), alongside a significant 22% reduction of the hazard of reaching a first event (hazard ratio [95% CI]: 0.78 [0.61, 0.99]; P = 0.045; Figure). Conclusions Mepolizumab as add-on treatment to inhaled triple therapy significantly reduces the risk of exacerbations requiring hospitalization in a wide spectrum of patients with COPD, with BEC starting from 150 cells/µL, compared with placebo. Funding GSK (117106/117113/208657). This abstract is funded by: GSK (117106/117113/208657)