Mepolizumab is Efficacious in Patients With Chronic Obstructive Pulmonary Disease Regardless of Airflow Obstruction Level: Post Hoc Analysis of the MATINEE Phase III Randomized Controlled Trial

Abstract Rationale: There is limited evidence on the clinical efficacy of biologics in patients with chronic obstructive pulmonary disease (COPD) and very severe airflow obstruction (GOLD grade 4). MATINEE assessed the efficacy of mepolizumab, a humanized monoclonal antibody specifically targeting interleukin-5, in patients with COPD and postbronchodilator forced expiratory volume in 1 second (FEV1) ≤80% and >20%. Methods: MATINEE (NCT04133909) was a Phase III randomized, placebo-controlled, parallel-group trial that enrolled patients with COPD, a history of recurrent moderate or severe exacerbations, and screening blood eosinophil count ≥300 cells/µL. Patients aged ≥40 years were randomized 1:1 to mepolizumab 100 mg, administered subcutaneously every 4 weeks for 52-104 weeks, or placebo, in addition to optimal inhaled triple therapy (dual long-acting bronchodilators plus inhaled corticosteroid [fluticasone propionate ≥500 μg/day or equivalent]). Airflow obstruction was categorized based on postbronchodilator FEV1 at screening, defined by GOLD guidelines (Table). Here we report on the prespecified subgroup analysis of the annualized rate of moderate/severe exacerbations (‘moderate’: treated with systemic corticosteroids and/or antibiotics; ‘severe’: requiring hospitalization ≥24 hours or resulting in death), alongside post hoc subgroup analysis of exacerbations requiring emergency department (ED) visit and/or hospitalization, Week 52 change from baseline and proportion of responders in the St George's Respiratory Questionnaire for COPD (SGRQ; ‘response’: ≥4-point improvement). Results: Airflow obstruction distribution by GOLD severity grade at screening was: 349 moderate (168 mepolizumab/181 placebo); 340 severe (180/160); 110 very severe (53/57). The annualized rate of moderate/severe exacerbations was lower with mepolizumab versus placebo, with the greatest difference of 27% observed in the severe subgroup (rate ratio [95% confidence interval (CI)]: 0.73 [0.57, 0.94]; Table). Exacerbations requiring ED visit and/or hospitalization were 32% (0.68 [0.40, 1.17]) and 31% (0.69 [0.26, 1.86]) lower with mepolizumab versus placebo in the severe and very severe subgroups, respectively (Table). At Week 52, SGRQ total score had numerically decreased from baseline across all airflow categories and treatment arms, with mepolizumab demonstrating greater reductions versus placebo in the moderate and severe subgroups (Table). The proportion of SGRQ responders favored mepolizumab versus placebo in the moderate airflow category only, with 58% higher response odds (odds ratio [95% CI]: 1.58 [1.01, 2.48]); there were no notable differences in the other subgroups (Table). Conclusions: Mepolizumab improved exacerbation rates in patients with COPD across GOLD grades 2, 3, and 4. Greatest SGRQ score improvements were observed in patients with GOLD grade 2 compared with 3 and 4.

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