Mepolizumab for COPD with Eosinophilic Phenotype following Hospitalization.

Background: Admission to hospital with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with a high risk of morbidity and mortality. Biologic treatment reduces COPD exacerbations in patients with eosinophilic inflammation. Mepolizumab, a monoclonal antibody to interleukin 5, reduces eosinophilic inflammation, but its effects on future hospitalization and mortality are uncertain.

Methods: In this phase 2b, double-blind, placebo-controlled trial, we randomly assigned patients hospitalized with an AECOPD and a blood eosinophil count greater than or equal to 300 cells/μl any time in the preceding 12 months to receive either mepolizumab 100 mg or placebo every 4 weeks for 48 weeks, with treatment initiated at hospital discharge. The primary end point was the time to readmission or death from any cause. Key secondary end points included the number of hospital readmissions, exacerbations, and health-related quality of life.

Results: A total of 238 patients were randomly assigned. The median time to hospitalization or death due to any cause was 25.4 weeks and 26.1 weeks in the mepolizumab and placebo groups, respectively, with Kaplan-Meier estimates of 33.9% and 31.0%, respectively (hazard ratio, 0.96; 95% confidence interval [CI], 0.70 to 1.32; P=0.811). The adjusted mean number of hospital readmissions was 1.65 (95% CI, 1.25 to 2.05) with mepolizumab and 1.85 (95% CI, 1.42 to 2.29) with placebo (risk ratio, 0.89; 95% CI, 0.64 to 1.25). The adjusted mean number of moderate or severe exacerbations was 2.80 (95% CI, 2.36 to 3.23) with mepolizumab and 3.45 (95% CI, 2.94 to 3.95) with placebo (risk ratio 0.81; 95% CI, 0.66 to 1.00). The numbers of adverse events and serious adverse events were similar between groups. No serious adverse event was attributed to the intervention.

Conclusions: Patients hospitalized with an AECOPD and eosinophilic inflammation of greater than 300 cells/μl of blood within the prior 12 months, had no benefit in risk of time to readmission or death following treatment with mepolizumab for 48 weeks. The observed change in moderate or severe exacerbations, which included the null in the upper bound of the 95% confidence interval, was in the direction observed in previous trials. (Funded by GSK plc; ClinicalTrials.gov number, NCT04075331.).