Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio.
Department of Internal Medicine, Erasmus Hospital, Free University of Brussels, Brussels, Belgium.
J Allergy Clin Immunol Pract. 2022 Sep;10(9):2367-2374.e3. doi: 10.1016/j.jaip.2022.04.037. Epub 2022 May 12.
Mepolizumab, an anti-interleukin-5 (IL-5) antibody, reduces disease flares in patients with hypereosinophilic syndrome (HES). Factors predicting treatment response are unknown.
To assess mepolizumab efficacy by baseline blood eosinophil count (BEC) and serum IL-5 level in patients with HES.
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).
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%).
Mepolizumab was efficacious in the patients with HES studied, irrespective of baseline BEC. Undetectable IL-5 levels should not preclude mepolizumab treatment.
美泊利珠单抗是一种抗白细胞介素-5（IL-5）的抗体，可减少嗜酸性粒细胞增多症（HES）患者的疾病发作。目前尚不清楚预测治疗反应的因素。
评估 HES 患者基线血液嗜酸性粒细胞计数（BEC）和血清 IL-5 水平对美泊利珠单抗的疗效。
本研究为评估美泊利珠单抗治疗 HES 的 III 期研究的事后分析（NCT02836496）。12 岁及以上，嗜酸性粒细胞增多症≥6 个月，前 1 年≥2 次发作，筛选时 BEC≥1000 个细胞/μL 的患者按 1:1 随机分组，分别接受每周 1 次皮下注射美泊利珠单抗（300mg）或安慰剂，联合基线嗜酸性粒细胞增多症治疗，共 32 周。分析基线 BEC（<1500/≥1500 至<2500/≥2500 细胞/μL）和基线血清 IL-5（<7.81/≥7.81pg/mL）对治疗 32 周时患者出现 1 次或多次发作的比例、年发作率及基线Brief Fatigue Inventory（BFI）第 3 项（32 周）的变化率的影响。
根据基线 BEC 亚组，美泊利珠单抗使患者出现 1 次或多次发作的比例降低了 63%至 90%，年发作率降低了 58%至 84%（治疗与嗜酸性粒细胞的交互作用 P=0.76 和 P=0.90）；与安慰剂相比，美泊利珠单抗可改善 BFI 第 3 项评分（细胞/μL：<1500：54% vs 37%；≥1500 至<2500：47% vs 31%；≥2500：61% vs 0%；治疗与嗜酸性粒细胞的交互作用 P=0.42）。大多数患者基线血清 IL-5 水平无法检测到；在这些患者中，美泊利珠单抗使患者出现 1 次或多次发作的比例（77%）和年发作率（67%）降低。
美泊利珠单抗对本研究中的 HES 患者有效，与基线 BEC 无关。无法检测到 IL-5 水平不应排除使用美泊利珠单抗治疗。
