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

Abstract Rationale: Chronic obstructive pulmonary disease (COPD) diagnosis and initiation of therapy are frequently delayed, which may cause chronic inflammation resulting in irreversible lung damage, limiting treatment efficacy. MATINEE assessed the efficacy of mepolizumab, a humanized monoclonal antibody specifically targeting interleukin-5, a central type 2 inflammatory cytokine, in patients with COPD with a wide spectrum of airflow obstruction and disease duration. Post hoc analyses were performed to determine whether previous disease duration is associated with treatment response. Methods: MATINEE (NCT04133909) was a Phase III randomized, parallel-group trial in patients with COPD, a history of recurrent moderate or severe exacerbations, and screening blood eosinophil count ≥300 cells/µL. Patients were randomized 1:1 to mepolizumab 100 mg, administered subcutaneously every 4 weeks for 52-104 weeks, or placebo, in addition to background inhaled triple therapy. Subgroups were defined by median time since COPD diagnosis (<9/≥9 years). We report the annualized rate of moderate/severe exacerbations (‘moderate’: treated with systemic corticosteroids and/or antibiotics; ‘severe’: requiring hospitalization ≥24 hours or resulting in death), exacerbations requiring emergency department (ED) visit and/or hospitalization, time to first exacerbation, and proportion of responders at Week 52 in the St. George's Respiratory Questionnaire for COPD (SGRQ; ≥4-point improvement) and COPD assessment test (CAT; ≥2-unit improvement). Results: Of 804 randomized and treated patients (403 mepolizumab), 375 had <9 years (182 mepolizumab) and 429 had ≥9 years (221 mepolizumab) COPD duration. Annualized rates of moderate/severe exacerbations were lower with mepolizumab than placebo by 19% in the <9 years (rate ratio [95% confidence interval (CI)]: 0.81 [0.62, 1.06]) and 24% in the ≥9 years subgroups (0.76 [0.60, 0.97]). Rates of exacerbations requiring ED visit and/or hospitalization were lower with mepolizumab than placebo, particularly in the ≥9 years subgroup (0.55 [0.32, 0.93]) compared with the <9 years subgroup (0.87 [0.49, 1.54]). The probability of experiencing a moderate/severe exacerbation by Week 104 was also lower with mepolizumab than placebo in both subgroups. The proportion of SGRQ responders (odds ratio [95% CI]) for mepolizumab versus placebo was 55% versus 47% in the <9 years (1.31 [0.85, 2.02]) and 46% versus 44% in the ≥9 years subgroup (1.08 [0.72, 1.61]); the proportion of CAT responders was similar between mepolizumab and placebo (Table). Conclusions: In this post hoc analysis, mepolizumab reduced exacerbation rates versus placebo, regardless of time since COPD diagnosis.Further data are needed to confirm if prompt treatment with mepolizumab results in better patient-reported outcomes.

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