Clinical Edge

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Assessing Mepolizumab for Eosinophilic COPD

N Engl J Med; ePub 2017 Oct 26; Pavord, et al

Among patients with chronic obstructive pulmonary disease (COPD) and an eosinophilic phenotype, mepolizumab (100 mg) was associated with a lower annual rate of moderate or severe exacerbations than placebo, a recent study found. The study also suggests that eosinophilic airway inflammation contributes to COPD exacerbations. Two phase 3, randomized, placebo-controlled, double-blind, parallel group trials were performed comparing mepolizumab (100 mg in METREX, 100 or 300 mg in METREO) with placebo, given as subcutaneous injection every 4 weeks for 52 weeks in patients with COPD with a history of moderate to severe exacerbations while taking inhaled glucocorticoid-based triple maintenance therapy. Researchers found:

  • In METREX, the mean annual rate of moderate or severe exacerbations in the modified intention-to-treat population with an eosinophilic phenotype (n=462 patients) was 1.40 per year in the mepolizumab group vs 1.71 per year in the placebo group (rate ratio, 0.82).
  • In METREO, the mean annual rate of moderate or severe exacerbations was 1.19 per year in the 100-mg mepolizumab group, 1.27 per year in the 300-mg mepolizumab group, and 1.49 per year in the placebo group.
  • The rate ratios for exacerbations in the 100-mg and 300-mg mepolizumab groups vs the placebo group were 0.80 and 0.86, respectively.

Citation:

Pavord ID, Chanez P, Criner GJ, et al. Mepolizumab for eosinophilic chronic obstructive pulmonary disease. N Engl J Med. 2017;377:1613-1629. doi:10.1056/NEJMoa1708208.

Commentary:

COPD is the only one of the top 5 causes of mortality in the US that is continuing to increase in incidence. Our therapies for COPD, including inhaled beta-agonists, inhaled anti-muscarinic agents, and inhaled steroids, are effective in decreasing the frequency of exacerbations, improving airflow, and improving quality of life. Unfortunately, many patients with severe COPD still have frequent exacerbations, even on triple therapy. It turns out that 40% of patients with COPD have high levels of eosinophils, defined as a peripheral-blood differential eosinophil count of >2%. These patients are described as having a eosinophilic phenotype COPD.1 Patients with an eosinophilic phenotype have an increased risk of COPD exacerbation. Mepolizumab, a humanized monoclonal antibody, reduces eosinophil counts in blood. It has been demonstrated to have efficacy for the treatment of eosinophil phenotype asthma.2 The study above represents both a practical and conceptual advance in the treatment of COPD, opening up the possibility of stratifying next step treatment according to eosinophil count in patients who continue to have exacerbations of COPD on triple therapy. —Neil Skolnik, MD

  1. Singh D, Kolsum U, Brightling CE, Locantore N, Agusti A, Tal-Singer R. Eosinophilic inflammation in COPD: Prevalence and clinical characteristics. Eur Respir J. 2014;44:1697-1700.
  2. Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371:1198-1207. doi:10.1056/NEJMoa1403290.