In pooled phase 3 data, mepolizumab lowered mean yearly systemic corticosteroid exposure by 178.97 mg in patients with a BEC of ≥150 cells/µL.
Mepolizumab (Nucala) reduced total yearly systemic corticosteroid (SCS) exposure, particularly high-dose courses, in patients with
Although treatment guidelines recommend SCS for COPD exacerbations, these agents are associated with complications in this population, prompting interest in targeted therapies capable of limiting their use.¹ Mepolizumab, a humanized monoclonal antibody targeting interleukin-5 (IL-5), is approved for patients with COPD and an eosinophilic phenotype. The pooled analysis examined SCS use across blood eosinophil count (BEC) thresholds of ≥ 150 cells/µL and ≥300 cells/µL.¹
“Mepolizumab can serve as an add-on to inhaled triple therapy and may reduce SCS burden in COPD, particularly complications associated with short-term high-dose courses, across a wide spectrum of screening BEC levels,” said lead author Nicola Hanania, MD, director of the American Lung Association Airways Clinical Research Center (ACRC) at the Baylor College of Medicine, in a statement.²
Hanania and colleagues pooled data from 3 randomized, placebo-controlled phase 3 trials: METREX, METREO, and MATINEE.¹ Eligible patients were aged ≥ 40 years with a COPD diagnosis of ≥ 1 year, Global Initiative for Chronic Obstructive Lung Disease grade 2 to 4 airflow obstruction, a history of exacerbations, and no current asthma diagnosis. All patients were receiving inhaled triple therapy and received mepolizumab 100 mg subcutaneously or placebo every 4 weeks for 52 weeks (METREX, METREO) or up to 104 weeks (MATINEE).¹
METREX enrolled patients regardless of BEC, METREO required a screening BEC of ≥ 150 cells/µL (or ≥300 cells/µL in the prior year), and MATINEE required a screening BEC of ≥ 300 cells/µL (and ≥ 150 cells/µL in the prior year).¹ SCS doses were converted to prednisolone equivalents and stratified as low (< 20 mg/day) or high (≥ 20 mg/day).¹
Of 2089 patients enrolled (1043 mepolizumab, 1046 placebo), 1713 had a BEC of ≥ 150 cells/µL and 1144 had a BEC of ≥300 cells/µL.¹ In the ≥ 150 cells/µL group, mean total SCS exposure was 434.64 mg/year with mepolizumab vs 609.95 mg/year with placebo (mean difference, 178.97 mg/year; 95% CI, 62.09–292.19).¹ In the ≥300 cells/µL group, mean exposure was 354.28 mg/year vs 551.52 mg/year, respectively (mean difference, 193.58 mg/year; 95% CI, 84.01–306.80).¹
Among patients with a BEC of ≥ 150 cells/µL, 57% received SCS for any cause, as did 55% of those with a BEC of ≥ 300 cells/µL.¹ The mean percentage of days not receiving SCS was 89.8% with mepolizumab vs 88.3% with placebo in the ≥150 cells/µL group and 90.8% vs 88.9% in the ≥300 cells/µL group.¹
The between-group difference centered on high-dose courses. In the ≥ 150 cells/µL group, the mean percentage of days on high-dose SCS was 4.5% with mepolizumab vs 5.9% with placebo, and low-dose days were identical at 5.7% in both arms.¹ In the ≥300 cells/µL group, high-dose days were 3.8% vs 5.1%, and low-dose days were 5.4% vs 6.1%.¹
Investigators concluded mepolizumab reduced total yearly SCS exposure compared with placebo regardless of whether patients met the ≥150 cells/µL or ≥300 cells/µL screening threshold.
Full results will be presented in the Precision COPD: Type 2 Inflammation, Biomarkers, and Targeted Therapy rapid fire original investigation session at CHEST 2026 on Tuesday, October 20, from 1:45 pm to 2:30 pm MST.²
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