Efficacy and safety of mepolizumab in hypereosinophilic syndrome: a Phase III, randomized, placebo-controlled trial

<div>Background</div><div>Anti-interleukin-5 therapy is a potential treatment for patients with hypereosinophilic syndrome (HES), although its clinical efficacy is unclear.background</div><div>Objective</div><div>To investigate the clinical efficacy and safety of mepolizumab versus placebo in patients with HES.</div><div>Methods</div><div>This randomized, multicenter, double-blind, placebo-controlled, Phase III trial was conducted across 39 centers in 13 countries. Eligible patients had FIP1L1-PDGFRA-negative HES, experienced ≥2 flares (worsening of HES-related symptoms or blood eosinophil count requiring therapeutic escalation) in the previous 12 months and had a screening blood eosinophil count ≥1000 cells/μL. Patients were randomized (1:1) to subcutaneous mepolizumab (300 mg) or placebo every 4 weeks for 32 weeks, plus existing HES therapy. The primary outcome was the proportion of patients with ≥1 flare (worsening of HES-related symptoms necessitating therapy escalation or ≥2 courses of blinded rescue oral corticosteroids) during the study; in addition, patients who withdrew early from the study were counted as having a flare. Safety endpoints were also assessed.</div><div>Results</div><div>The proportion of patients experiencing ≥1 flare/withdrawing from the study was 50% lower with mepolizumab versus placebo (15/54 [28%] vs 30/54 [56%]; p=0.002). Logistic regression analysis was consistent with the primary analysis (odds ratio: 0.28; 95% confidence interval: 0.12, 0.64; p=0.003). Similar proportions of patients in the mepolizumab and placebo groups experienced on-treatment adverse events (48/54 [89%] vs 47/54 [87%]).results</div><div>Conclusion</div><div>Compared with placebo, mepolizumab significantly reduced the occurrence of flares in patients with HES, with no new safety signals identified.conclusion</div>