A34-21 Disease Stability Is Achievable in a Wide Spectrum of Patients With Chronic Obstructive Pulmonary Disease Receiving Mepolizumab: Pooled Results From Phase III Randomized Controlled Trials

Rationale Chronic obstructive pulmonary disease (COPD) activity includes exacerbations, which drive disease progression, characterized by worsening symptoms and deteriorating lung function. Disease stability, defined as a sustained state of low disease activity following optimization of management, is an emerging, ambitious and achievable treatment goal in COPD. Mepolizumab is an approved add-on maintenance treatment for adults with COPD and an eosinophilic phenotype, with proven efficacy in several Phase III randomized, controlled trials (RCTs). This pooled analysis assessed the effect of mepolizumab on disease stability in COPD. Methods METREX (GSK ID: 117106/ClinicalTrials.gov identifier: NCT02105948), METREO (117113/NCT02105961), and MATINEE (208657/NCT04133909) were Phase III RCTs assessing the efficacy of mepolizumab 100 mg versus placebo in patients with COPD, a history of exacerbations, and receiving triple therapy. This pooled post hoc analysis in patients with blood eosinophil count (BEC) ≥300 cells/µL at screening, evaluated disease stability in the overall population (N = 1146) and by Global Initiative for Chronic Obstructive Lung Disease (GOLD) status. Disease stability at Week 52 was defined as a three-component composite endpoint of 1) no moderate/severe exacerbations (‘exacerbations’); 2) ≤0 change from baseline in COPD Assessment Test scores (‘health status’); 3) ≥0mL change from baseline in forced expiratory volume in 1 second (‘lung function’). Results At Week 52, disease stability was achieved by more patients receiving triple therapy treated with mepolizumab versus placebo (18% [102/568] vs 15% [84/578]). Among the individual components, exacerbations were the most prominent driver of the numerical difference in achieving disease stability between groups, with the following rates of achieving disease stability criteria: exacerbations (52% [295/568] vs 42% [242/578]); health status (54% [309/568] vs 53% [306/578]) and lung function (45% [256/568] vs 43% [247/578]). There were more patients achieving disease stability with mepolizumab versus placebo across all GOLD subgroups (GOLD 2: 26% vs 23%, GOLD 3: 11% vs 9%, and GOLD 4: 16% vs 6%) (Figure). Conclusions Patients with COPD and BEC ≥300 cells/µL receiving triple therapy treated with mepolizumab achieved disease stability in greater proportions than those receiving placebo. Disease stability is therefore achievable with mepolizumab in patients otherwise poorly controlled on triple therapy, with a wide spectrum of COPD presentations.