Mepolizumab provides a small reduction in the exacerbations of moderate to severe eosinophilic COPD

Reference

Pavord ID, Chanez P, Criner GJ, et al. Mepolizumab for eosinophilic chronic obstructive pulmonary disease. N Engl J Med 2017;377(17):1613-1629.

Synopsis

The current guideline-recommended therapy for patients with moderate to severe COPD is the combination of an inhaled glucocorticoid, inhaled long-acting beta-agonist, and an inhaled antimuscarinic agent like tiotropium. This study identified patients who had experienced 2 or more moderate exacerbations or at least one severe exacerbation in the previous 12 months despite using the recommended regimen. All study participants also had a post-bronchodilator FEV1 of between 20% and 80% of predicted. This report describes the results of 2 similar trials. In the METREX trial, patients were stratified by eosinophil count, and in the METREO trial only those with eosinophilia were enrolled. Analysis was by modified intention to treat, including all patients who received one dose of the study medication. In the METREX trial, 836 patients were randomized to receive the monoclonal antibody mepolizumab 100 mg every 4 weeks for 1 year, while in the METREO trial 674 patients were randomized to receive either mepolizumab 100 mg, mepolizumab 300 mg, or placebo injection, also every 4 weeks for 1 year. Other than eosinophil counts, groups were balanced and the participants had a mean age of 65 years with a mean FEV1 percent predicted of 45%. Since there were 2 trials, with different subgroups and a multiplicity of outcomes, the results are complex. The primary outcome was the number of moderate or severe exacerbations during the study period. This was not significantly different in the overall METREX and METREO populations. In the subgroup of patients with > 300 eosinophils/mm3, there was a small reduction in the likelihood of an exacerbation (1.40 vs 1.71 per year; rate ratio 0.82; 95% CI 0.68 - 0.98). There was no difference in adverse events or harms between groups.