Pavord ID, et al. - Here, researchers assess the effectiveness and safety of subcutaneous mepolizumab, as compared with placebo, as an add-on to triple inhaled therapy in patients with chronic obstructive pulmonary disease (COPD) who had an eosinophilic phenotype and a history of moderate or severe exacerbations, and also the phenotypes of patients who are probably going to have a response to mepolizumab treatment. Among patients with COPD who were already receiving maximal inhaled glucocorticoid-based triple inhaled maintenance therapy, mepolizumab resulted in lower rates of moderate or severe exacerbations than placebo and in longer times to a first exacerbation, and the extent of these impacts was identified with blood eosinophil count. With the utilization of mepolizumab as a targeted treatment to decrease blood eosinophil counts, these trials demonstrate the significance of blood eosinophils in COPD exacerbations.

Methods

• For this study, they performed two phase 3, randomized, placebo-controlled, double-blind, parallel-group trials.
• This study compared mepolizumab (100 mg in METREX, 100 or 300 mg in METREO) with placebo, given as a subcutaneous injection every 4 weeks for 52 weeks in patients with COPD who had a history of moderate or severe exacerbations while taking inhaled glucocorticoid-based triple maintenance therapy.
• In METREX, unselected patients in the modified intention-to-treat population with an eosinophilic phenotype were stratified according to blood eosinophil count (≥ 150 per cubic millimeter at screening or ≥ 300 per cubic millimeter amid the previous year).
• In METREO, all patients had a blood eosinophil count of at least 150 per cubic millimeter at screening or at least 300 per cubic millimeter amid the previous year.
• The annual rate of moderate or severe exacerbations was the primary endpoint.
• They also assessed safety.

Results

• In METREX, the mean annual rate of moderate or severe exacerbations in the modified intention-to-treat population with an eosinophilic phenotype (462 patients) was 1.40 per year in the mepolizumab group versus 1.71 per year in the placebo group (rate ratio, 0.82; 95% confidence interval [CI], 0.68 to 0.98; adjusted P=0.04); no significant between-group differences were seen in the overall modified intention-to-treat population (836 patients) (rate ratio, 0.98; 95% CI, 0.85 to 1.12; adjusted P>0.99).
• 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 versus the placebo group were 0.80 (95% CI, 0.65 to 0.98; adjusted P=0.07) and 0.86 (95% CI, 0.70 to 1.05; adjusted P=0.14), respectively.
• A greater impact of mepolizumab, as compared with placebo, on the annual rate of moderate or severe exacerbations was seen among patients with higher blood eosinophil counts at screening.
• The safety profile of mepolizumab was similar to that of placebo.