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Chronic obstructive pulmonary disease (COPD) is a common disease characterized by progressive airflow obstruction, chronic inflammation in the lungs, and the occurrence of persistent symptoms and acute exacerbations.1 Up to 40% of patients with COPD have an eosinophilic phenotype, defined as a peripheral-blood differential eosinophil count of 2% or more, which equates to approximately 150 to 200 eosinophils per cubic millimeter.2,3 Blood eosinophil counts of this level are associated with an increased risk of COPD exacerbations; the risk can be partially mitigated by long-term treatment with inhaled glucocorticoids.4,5 Moreover, these patients have a good response to treatment of acute exacerbations with oral glucocorticoids.6,7 These findings are consistent with a pathogenic role for eosinophils in exacerbations of COPD and provide a strong rationale for therapies that specifically inhibit eosinophilic inflammation.
Current Global Initiative for Chronic Obstructive Lung Disease (GOLD) treatment guidelines for COPD recommend maintenance use of triple inhaled therapy that includes a combination of inhaled glucocorticoids, long-acting β2-agonists, and long-acting muscarinic-receptor antagonists in patients with frequent exacerbations who do not have adequate outcomes with other treatments.1 However, approximately 30 to 40% of patients are reported to continue to have moderate or severe exacerbations despite receiving triple inhaled therapy.8,9
Mepolizumab, a humanized monoclonal antibody, reduces eosinophil counts in blood and tissues by blocking interleukin-5, a key eosinophil cytokine, through binding to eosinophil surface receptors.10,11 In patients with severe eosinophilic asthma, mepolizumab treatment has been found to be associated with lower rates of exacerbations and symptoms and with greater improvements in health-related quality of life than placebo and the existing standard of care.12–14 In post hoc analyses of data from the Mepolizumab as Adjunctive Therapy in Patients with Severe Asthma (MENSA) and Dose Ranging Efficacy and Safety with Mepolizumab in Severe Asthma (DREAM) trials, mepolizumab was also associated with lower exacerbation rates than placebo among patients who had severe eosinophilic asthma with clinical features of COPD.12,13,15
The objective of the Mepolizumab vs. Placebo as Add-on Treatment for Frequently Exacerbating COPD Patients (METREX) and Mepolizumab vs. Placebo as Add-on Treatment for Frequently Exacerbating COPD Patients Characterized by Eosinophil Level (METREO) trials...