Patients with chronic obstructive pulmonary disease (COPD) require 29% to 36% less systemic corticosteroid therapy when treated with mepolizumab as an add-on to inhaled triple therapy, according to a pooled analysis presented on October 20 at the American College of Chest Physicians annual meeting in Phoenix.
Clinical guidelines often rely on systemic corticosteroids to manage COPD exacerbations, but these medications carry risks such as fractures, sepsis, hyperglycemia, and venous thromboembolism. Nicola A. Hanania, MD, MS, director of the Airway Clinical Research Center at Baylor College of Medicine, said that reducing the reliance on these steroids remains a critical unmet need for patients.
“Mepolizumab is a humanized monoclonal antibody specifically targeting IL-5 [interleukin-5], approved in COPD with an eosinophilic phenotype,” Hanania told Medscape Medical News. “Mepolizumab has shown corticosteroid-sparing properties in other approved eosinophilic indications.”
The analysis aggregated data from three phase 3 trials—METREX, METREO, and MATINEE—involving 2,089 participants aged 40 or older. All patients had a history of exacerbations, airflow obstruction (GOLD grades 2-4), and had been diagnosed with COPD for at least one year.
Researchers compared 1,043 patients who received 100 mg of subcutaneous mepolizumab every four weeks against 1,046 patients receiving a placebo. The trials utilized different blood eosinophil count (BEC) thresholds, ranging from no specific criteria in METREX to a BEC of at least 300 cells/μL in the MATINEE study.
The study revealed that while the total number of steroid-free days remained similar between the groups, the frequency of high-dose corticosteroid use—defined as 20 mg or more per day—dropped among those on the biologic therapy.
In participants with a BEC of at least 150 cells/μL, those receiving mepolizumab experienced 4.5% of their days on high-dose steroids, compared with 5.9% for the placebo group. For patients with a BEC of at least 300 cells/μL, the high-dose exposure was 3.8% for the mepolizumab group versus 5.1% for placebo.
Geoffrey L. Chupp, MD, professor of medicine at the Yale School of Medicine, said that the findings provide clinicians with clarity regarding the use of eosinophil counts to guide treatment.
“The results demonstrate that both the 150 and 300 cell/μl cutoff are associated with reduced systemic steroid use compared to placebo, and the reduction is similar, albeit small, in this large pooled analysis,” Chupp told Medscape Medical News. “This is valuable information because there have been questions about what cutoff is best to use for starting mepolizumab or other biologics in patients with COPD.”
Though the pooled analysis suggests that both eosinophil thresholds can predict a positive response to the therapy, researchers have yet to determine which specific patient groups benefit most.
“I think it would be interesting to examine this pooled cohort to identify clinical phenotypic features in addition to baseline Eos counts,” Chupp said.
The therapy helps reduce the systemic corticosteroid burden for patients, specifically lowering the number of days requiring high-dose steroids, which are associated with complications like fractures and sepsis.
How do eosinophil counts affect treatment decisions?
Data from these trials indicate that both 150 cells/μL and 300 cells/μL cutoffs are associated with a reduced need for systemic steroids, helping clinicians identify which patients may respond best to biologics.
The three trials (METREX, METREO, and MATINEE) utilized different entry criteria regarding blood eosinophil counts, though the analysis showed a consistent reduction in steroid reliance across the pooled cohorts.