Mepolizumab Efficacy in COPD: Insights from Longitudinal Patterns of Blood Eosinophil Counts and Their Variability Across Three Clinical Trials

RATIONALE: Blood eosinophil count (BEC) is a biomarker indicating type 2 (T2) inflammation in patients with chronic obstructive pulmonary disease (COPD) but can be variable. OBJECTIVES: Evaluate mepolizumab efficacy in patients with COPD with variability of BEC patterns. METHODS: Data were pooled from Phase 3, randomized, double-blind, placebo-controlled METREX (NCT02105948), METREO (NCT02105961), and MATINEE (NCT04133909) trials. Patients receiving mepolizumab 100 mg or placebo were included. These trials documented historical BEC (within 12 months before randomization) for all patients. Outcomes included annualized rates of moderate or severe exacerbations, and exacerbations requiring an emergency department (ED) visit and/or hospitalization. Outcomes were assessed in subgroups based on BEC values in the 12 months before randomization, at screening, and at baseline. MEASUREMENTS AND MAIN RESULTS: Annualized rates of moderate or severe exacerbations were reduced, or trended towards reduction, with mepolizumab versus placebo in patients with T2 inflammation characteristics, including those with BEC ≥ 300 cells/µL at any pre-randomization timepoint (21% reduction), persistently elevated BECs (12-27% reduction), and variable BECs over time (22-36% reduction). Across various subgroups with elevated BEC, starting from ≥ 150 cells/µL, mepolizumab reduced exacerbations requiring ED visit and/or hospitalization. Patients with persistently low BEC (<150 cells/µL) experienced no benefit with mepolizumab. CONCLUSIONS: Mepolizumab improved exacerbation-related outcomes in patients with COPD and T2 inflammation, characterized by both consistently and intermittently elevated BEC. Persistent BEC elevation is not required to identify treatable eosinophilic phenotypes in COPD.