Mepolizumab Reduces Hypereosinophilic Syndrome Flares Irrespective of Blood Eosinophil Count and Interleukin-5

Background: Mepolizumab, an anti-interleukin-5 (IL-5) antibody, reduces disease flares in patients with hypereosinophilic syndrome (HES). Factors predicting treatment response are unknown. Objective: To assess mepolizumab efficacy by baseline blood eosinophil count (BEC) and serum IL-5 level in patients with HES. Methods: This post hoc analysis used data from the phase III study assessing mepolizumab in patients with HES (NCT02836496). Patients 12 years old or older, with HES for 6 or more months, 2 or more flares in the previous year, and BEC ≥1,000 cells/μL at screening were randomized (1:1) to 4-weekly subcutaneous mepolizumab (300 mg) or placebo, plus baseline HES therapy, for 32 weeks. The proportion of patients experiencing 1 or more flares (wk 32), annualized flare rate, and proportion of patients with change from baseline in Brief Fatigue Inventory (BFI) item 3 (wk 32), were analyzed by baseline BEC (<1500/≥1500 to <2500/≥2500 cells/μL). Flare outcomes were assessed by baseline serum IL-5 (<7.81/≥7.81 pg/mL). Results: Across baseline BEC subgroups, mepolizumab reduced the proportion of patients experiencing 1 or more flares by 63% to 90% and flare rate by 58% to 84% (treatment-by-eosinophil interaction P =.76 and P =.90, respectively); patients had improved BFI item 3 score with mepolizumab versus placebo (cells/μL: <1,500: 54% vs 37%; ≥1,500 to <2,500: 47% vs 31%; ≥2,500: 61% vs 0%; treatment-by-eosinophil interaction P =.42). Most patients had undetectable baseline serum IL-5 levels; among these, mepolizumab versus placebo reduced the proportion of patients with 1 or more flares (77%) and flare rate (67%). Conclusions: Mepolizumab was efficacious in the patients with HES studied, irrespective of baseline BEC. Undetectable IL-5 levels should not preclude mepolizumab treatment.