B32-48 Mepolizumab Reduces Type-2 COPD Exacerbations Requiring Systemic Corticosteroids in a Wide Spectrum of Patients: Pooled Results From Phase III Randomized Controlled Trials

Rationale

Systemic corticosteroids (SCS) are a cornerstone of treatment for chronic obstructive pulmonary disease (COPD) exacerbations, with an enhanced treatment response in patients with raised blood eosinophil counts (BEC) experiencing type 2 inflammation-driven exacerbations. Mepolizumab is a humanized monoclonal antibody specifically targeting interleukin-5, approved as an add-on to inhaled triple therapy for the treatment of patients with COPD with an eosinophilic phenotype.

Methods

We performed an 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 of GOLD grades 2-4 (Global Initiative for Chronic Obstructive Lung Diseases), and had no current diagnosis of asthma. In METREX/METREO prior moderate exacerbations were treated with SCS and/or antibiotics; in MATINEE prior moderate exacerbations had to be treated with SCS. 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 annualized rate of moderate/severe exacerbations (‘moderate’: treated as outpatient; ‘severe’: requiring hospitalization ≥24 hours or resulting in death) and those requiring emergency department (ED) visit and/or hospitalization, that were treated with SCS (with/without antibiotics). Outcomes were assessed 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 moderate/severe exacerbations treated with SCS was significantly reduced by 25% with mepolizumab versus placebo (rate ratio [RR] [95% confidence interval (CI)]: 0.75 [0.67, 0.85]; Table). Exacerbations requiring ED visit and/or hospitalization treated with SCS were also significantly reduced by 25% (RR [95% CI]: 0.75 [0.58, 0.97]; Table).

Conclusions

Mepolizumab as add-on to inhaled triple therapy in a wide spectrum of patients with COPD and an eosinophilic phenotype significantly reduces type 2 inflammation-related COPD exacerbations (i.e., treated with SCS).

Funding

GSK (117106/117113/208657).

This abstract is funded by: GSK (117106/117113/208657)