Mepolizumab Reduces the Risk of Severe Exacerbations and Healthcare Resource Utilization in Chronic Obstructive Pulmonary Disease: Results from the MATINEE Phase III Randomized Controlled Trial

Abstract Rationale: Patients with chronic obstructive pulmonary disease (COPD) and raised blood eosinophil counts (BEC) experience more frequent and severe exacerbations, which can lead to increased healthcare resource utilization (HCRU) and mortality. Mepolizumab is a humanized monoclonal antibody specifically targeting interleukin-5, a central cytokine in type 2 inflammation. Methods: The MATINEE (NCT04133909) Phase III, randomized, double-blind, parallel-group trial enrolled patients with COPD, BEC ≥300 cells/µL at screening, and a history of exacerbations despite receiving optimal inhaled triple therapy (dual long-acting bronchodilators plus inhaled corticosteroid [fluticasone propionate ≥500 μg/day or equivalent]). Patients ≥40 years of age were randomized 1:1 to mepolizumab 100 mg administered subcutaneously every 4 weeks for 52-104 weeks versus placebo, in addition to optimal inhaled triple therapy. This secondary analysis reports the time to first severe exacerbation (requiring hospitalization ≥24 hours or resulting in death) and to first exacerbation leading to emergency department (ED) visit and/or hospitalization, alongside the annualized rates and proportions of patients experiencing ≥1 of such exacerbations, and post hoc patient-reported HCRU, all up to Week 104. Results: Overall, 804 patients were randomized and treated (403 mepolizumab/401 placebo). Numerically lower proportions of mepolizumab-treated patients versus placebo experienced ≥1 severe exacerbation (11% vs 15%) and ≥1 exacerbation requiring ED visit and/or hospitalization (14% vs 18%; Table) by Week 104. With mepolizumab, compared with placebo, the annualized rate of severe exacerbations was 34% lower, alongside a 35% lower rate in exacerbations requiring ED visit and/or hospitalization (rate ratio [95% confidence interval (CI)] 0.66 [0.43, 1.01] and 0.65 [0.43, 0.96], respectively). The risk of experiencing a first severe exacerbation over 104 weeks was 26% lower with mepolizumab versus placebo (hazard ratio [95% CI]: 0.74 [0.50, 1.08]), alongside a 27% lower risk of a first exacerbation leading to ED visit and/or hospitalization (0.73 [0.51, 1.04]). Patient-reported HCRU resulting from exacerbations by Week 104 was similar in mepolizumab- and placebo-treated patients, as illustrated by the number of exacerbations requiring ED visits (11% vs 15%), urgent care/outpatient clinic visits (6% vs 6%), general ward admissions (12% vs 12%), and intensive care admissions (5% vs 4%). Mepolizumab-treated patients experienced lower mean resource utilization per exacerbation in ED visits, urgent care/outpatient clinic visits, and days in intensive care (Table). Conclusions: Mepolizumab as add-on treatment to optimal triple therapy may help prevent severe exacerbations and reduce subsequent healthcare burden in patients with COPD, compared with placebo.