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Mepolizumab Reduces Exacerbation Risk, Healthcare Resource Utilization in COPD
Gerard Criner, MD, reviews findings from a secondary analysis of the phase 3 MATINEE trial of mepolizumab and looks ahead to the potential significance of the drug, if approved.
Use of mepolizumab as an add-on treatment to optimal triple therapy may help prevent severe exacerbations and reduce subsequent healthcare burden in patients with chronic obstructive pulmonary disease (COPD), according to data from the phase 3 MATINEE trial presented at the American Thoracic Society (ATS) International Conference 2025.
“Patients with COPD who are plagued by frequent moderate or severe exacerbations may have type 2 inflammation,” Gerard Criner, MD, chair and professor of thoracic medicine and surgery at Lewis Katz School of Medicine at Temple University and director of the Temple Lung Center, explained to HCPLive. “In patients who continue to exacerbate despite maximal inhaled therapy with long acting bronchodilators and inhaled steroids, that presents an opportunity to have more robust, targeted treatments that selectively target type 2 inflammation.”
A humanized monoclonal antibody specifically targeting interleukin-5, a central cytokine in type 2 inflammation, mepolizumab’s use in COPD was explored in the randomized, double-blind, parallel-group MATINEE trial. It enrolled patients ≥ 40 years of age with COPD, blood eosinophil counts ≥300 cells/µL at screening, and a history of exacerbations despite receiving optimal inhaled triple therapy, defined as dual long-acting bronchodilators plus inhaled corticosteroid.
Participants were randomly assigned in a 1:1 ratio to mepolizumab 100 mg administered subcutaneously every 4 weeks for 52-104 weeks or placebo, in addition to optimal inhaled triple therapy. The secondary analysis presented at ATS reports the time to first severe exacerbation (requiring hospitalization ≥24 hours or resulting in death) and to first exacerbation leading to emergency department (ED) visit and/or hospitalization, alongside the annualized rates and proportions of patients experiencing ≥1 of such exacerbations, and post hoc patient-reported HCRU, all up to Week 104.
A total of 804 patients were randomized and treated, including 403 to mepolizumab and 401 to placebo. Results showed numerically lower proportions of mepolizumab-treated patients versus placebo experienced ≥1 severe exacerbation (11% vs 15%) and ≥1 exacerbation requiring ED visit and/or hospitalization (14% vs 18%) by Week 104. With mepolizumab, compared with placebo, the annualized rate of severe exacerbations was 34% lower, alongside a 35% lower rate in exacerbations requiring ED visit and/or hospitalization (rate ratio [RR], 0.66; 95% CI, 0.43-1.01 and RR, 0.65; 95% CI, 0.43-0.96, respectively).
Investigators noted the risk of experiencing a first severe exacerbation over 104 weeks was 26% lower with mepolizumab versus placebo (hazard ratio [HR], 0.74; 95% CI, 0.50-1.08), alongside a 27% lower risk of a first exacerbation leading to ED visit and/or hospitalization (HR, 0.73; 95% CI, 0.51-1.04).
Patient-reported HCRU resulting from exacerbations by Week 104 was similar in mepolizumab- and placebo-treated patients, as evidenced by the number of exacerbations requiring ED visits (11% vs 15%), urgent care/outpatient clinic visits (6% vs 6%), general ward admissions (12% vs 12%), and intensive care admissions (5% vs 4%). Mepolizumab-treated patients experienced lower mean resource utilization per exacerbation in ED visits, urgent care/outpatient clinic visits, and days in intensive care.
“I think that if this drug receives approval, this extends our knowledge into how type two inflammation affects patients with COPD and the long term benefits of this treatment, regardless if they have chronic bronchitis or emphysema,” Criner said.
Editors’ note: Criner has relevant disclosures with APREO, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Pfizer, Pulmonx, Sanofi, and others.
