A randomized, placebo-controlled phase III trial found that mepolizumab may reduce the frequency of moderate or severe exacerbations in patients with chronic obstructive pulmonary disease and an eosinophilic phenotype who were receiving triple inhaled therapy.
Mepolizumab is a monoclonal antibody designed to target interleukin (IL)-5, a cytokine involved in eosinophil production and survival. Elevated blood eosinophil levels, present in approximately 20% to 40% of patients with chronic obstructive pulmonary disease (COPD), are associated with an increased risk of exacerbation.
In the trial, researchers enrolled 804 participants across 25 countries. They included patients with blood eosinophil counts of at least 300 cells per μL. Eligible patients were at least 40 years old, had a history of frequent exacerbations, and were current or former smokers with a minimum 10 pack-year history. The participants were randomly assigned to receive 100 mg of mepolizumab or placebo via subcutaneous injection every 4 weeks for up to 104 weeks while continuing their existing triple inhaled therapy regimen.
The primary endpoint was the annualized rate of moderate or severe exacerbations. This rate was lower in the mepolizumab group compared with in the placebo group: 0.80 vs 1.01 events per year, yielding a rate ratio of 0.79 (95% confidence interval [CI] = 0.66–0.94, P = .01), representsing a 21% relative reduction.
Time to first exacerbation was also longer in the mepolizumab group. The median was 419 days compared with 321 days in the placebo group (hazard ratio = 0.77, 95% CI = 0.64–0.93, P = .009).
Exacerbations requiring emergency department visits or hospitalization occurred less frequently with mepolizumab compared with placebo (0.13 vs 0.20 events per year, rate ratio = 0.65, 95% CI = 0.43–0.96).
No statistically significant differences were observed between groups in patient-reported outcomes, including the COPD Assessment Test, St. George’s Respiratory Questionnaire, and the Evaluating Respiratory Symptoms in COPD scale.
Adverse events were reported in 74% of the mepolizumab group and 77% of the placebo group. Serious adverse events or mortality occurred in 25% and 28% of patients, respectively. Deaths occurred in 11 patients in each group. The most common adverse events were worsening COPD and SARS-CoV-2 infection.
Patients with a history of asthma were excluded from the study to isolate effects specific to COPD. The findings built on earlier trials of biologic therapies in eosinophilic COPD and suggested that targeted inhibition of IL-5 may reduce exacerbation frequency in appropriately selected patients.
Full disclosures are available in the published study.