Baseline blood eosinophil count as a predictor of treatment response to the licensed dose of mepolizumab in severe eosinophilic asthma.

Abstract

Previous analyses examining the relationship between blood eosinophil count and mepolizumab treatment effects in severe eosinophilic asthma have used a range of doses and administration routes. This post hoc meta-analysis included data from the MENSA (MEA115588/NCT01691521) and MUSCA (200862/NCT02281318) trials. Patients (≥12 years) with severe eosinophilic asthma who experienced ≥2 exacerbations in the prior year received either mepolizumab 100 mg subcutaneously (SC) or 75 mg intravenously, or placebo plus standard of care every 4 weeks. This meta-analysis reports data from patients receiving the licensed dose of mepolizumab (100 mg SC) or placebo only. The primary endpoint was the annual rate of clinically significant exacerbations; secondary endpoints included rate of exacerbations requiring hospitalization/emergency room (ER) visit, proportion of patients with no clinically significant exacerbations, and changes from baseline in forced expiratory volume in 1 s, Asthma Control Questionnaire-5 and St George's Respiratory Questionnaire scores. Analyses were stratified by baseline blood eosinophil count (<150, ≥150, ≥300, ≥400, ≥500, ≥750, ≥1000, ≥150-<300, or ≥300-<500 cells/μL). Mepolizumab reduced annual clinically significant exacerbation rates by 45%-85%, exacerbations requiring hospitalization/ER visit by 60%-70%, and increased the odds of no clinically significant exacerbations across all eosinophil threshold subgroups versus placebo, and improved all other secondary endpoints in subgroups ≥150 cells/μL. Greater treatment effects with increasing blood eosinophil count were observed. Mepolizumab demonstrated consistent clinical benefits in patients with baseline blood eosinophil counts ≥150 cells/μL, confirming the suitability of this cut-off for identifying patients responsive to the licensed mepolizumab dose.