Research Summary

Mepolizumab Reduces Exacerbations in COPD With Eosinophilic Phenotype

Anthony Calabro, MA

Key Highlights

  • Mepolizumab reduced the annualized rate of moderate or severe chronic obstructive pulmonary disease exacerbations compared with placebo.
  • The median time to first moderate or severe exacerbation was longer with mepolizumab (419 days vs 321 days).
  • There was no significant improvement in quality of life or symptom scores was observed.

In a phase 3 trial of patients with chronic obstructive pulmonary disease (COPD) characterized by an eosinophilic phenotype, subcutaneous mepolizumab reduced the annualized rate of moderate or severe exacerbations compared with placebo.1 Patients receiving mepolizumab experienced fewer exacerbations and a longer time to first exacerbation, while no significant differences were observed in patient-reported outcomes.

Eosinophilic inflammation, present in up to 40% of patients with COPD2, is associated with a higher risk of exacerbations. Mepolizumab, a monoclonal antibody targeting interleukin-5, has previously shown benefits in eosinophilic asthma, but little is known about its potential role in eosinophilic COPD. To fill this gap, researchers conducted a double-blind, randomized, placebo-controlled phase 3 trial involving 804 patients with COPD who had a history of exacerbations and a blood eosinophil count of 300 cells/μL or greater, despite receiving triple inhaled therapy.

Participants were randomized 1:1 to receive either 100 mg of mepolizumab or placebo every 4 weeks for a duration of 52 to 104 weeks. The primary endpoint was the annualized rate of moderate or severe exacerbations. Secondary endpoints included time to first moderate or severe exacerbation, quality of life measures, symptom scores, and rates of exacerbations requiring emergency care or hospitalization.

Among the 804 participants, those treated with mepolizumab (n = 403) experienced a significantly lower annualized rate of moderate or severe exacerbations than those who received placebo (n = 401), at 0.80 vs 1.01 events per year (rate ratio, 0.79; 95% CI, 0.66-0.94; P = .01). The median time to first moderate or severe exacerbation was 419 days in the mepolizumab group vs 321 days in the placebo group (hazard ratio, 0.77; 95% CI, 0.64-0.93; P = .009). However, no significant differences were noted between groups in measures of health-related quality of life or symptoms, and subsequent secondary endpoint testing was not pursued due to the hierarchical analysis plan. The incidence of adverse events was comparable between groups.

“Treatment with mepolizumab led to a lower annualized rate of moderate or severe exacerbations when added to background triple inhaled therapy among patients with COPD and an eosinophilic phenotype,” the authors concluded.

References

  1. Sciurba FC, Criner GJ, Christenson SA, et al. Mepolizumab to prevent exacerbations of COPD with an eosinophilic phenotype. N Engl J Med. 2025;392(17):1710-1720. doi:10.1056/NEJMoa2413181
  2. Ortega H, Llanos JP, Lafeuille MH, et al. Burden of disease associated with a COPD eosinophilic phenotype. Int J Chron Obstruct Pulmon Dis. 2018;13:2425-2433. Published 2018 Aug 13. doi:10.2147/COPD.S170995