Efficacy and safety of mepolizumab in hypereosinophilic syndrome: A phase III, randomized, placebo-controlled trial.
Efficacy and safety of mepolizumab in hypereosinophilic syndrome: A phase III, randomized, placebo-controlled trial.
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DOI：
10.1016/j.jaci.2020.08.037
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发表时间：
2020-12
影响因子：
14.2
通讯作者：
Gleich, Gerald J.
中科院分区：
文献类型：
--
作者：
Roufosse, Florence;Kahn, Jean-Emmanuel;Rothenberg, Marc E.;Wardlaw, Andrew J.;Klion, Amy D.;Kirby, Suyong Yun;Gilson, Martyn J.;Bentley, Jane H.;Bradford, Eric S.;Yancey, Steven W.;Steinfeld, Jonathan;Gleich, Gerald J.
抗il -5治疗是高嗜酸性粒细胞综合征（HES）患者的潜在治疗方法，尽管其临床疗效尚不清楚。我们试图研究mepolizumab与安慰剂在HES患者中的临床疗效和安全性。这项随机、多中心、双盲、安慰剂对照的III期试验在13个国家的39个中心进行。符合条件的患者为fip1l1 - pdgfr阴性HES，在过去12个月内经历2次或以上的发作（HES相关症状恶化或血液嗜酸性粒细胞计数需要增加治疗），并且筛查的血液嗜酸性粒细胞计数大于或等于1000细胞/μL。患者每4周随机（1:1）接受皮下mepolizumab （300 mg）或安慰剂治疗，共32周，加上现有的HES治疗。主要结局是研究期间出现1次或1次以上急性发作（hes相关症状恶化需要升级治疗或≥2个盲法口服皮质类固醇治疗疗程）的患者比例；此外，早期退出研究的患者被视为有发作。安全终点也被评估。与安慰剂相比，mepolizumab组出现1次或1次以上急性发作/退出研究的患者比例降低了50%（54例中有15例[28%]vs 54例中有30例[56%]；P = 0.002）。Logistic回归分析与初步分析一致（优势比0.28;95% CI 0.12-0.64; P = 0.003）。mepolizumab组和安慰剂组患者在治疗期间出现不良事件的比例相似（54例中有48例[89%]vs 54例中有47例[87%]）。与安慰剂相比，mepolizumab显著降低HES患者的耀斑发生率，未发现新的安全性信号。
Anti–IL-5 therapy is a potential treatment for patients with hypereosinophilic syndrome (HES), although its clinical efficacy is unclear. We sought to investigate the clinical efficacy and safety of mepolizumab versus placebo in patients with HES. 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 or more 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 greater than or equal to 1000 cells/μL. Patients were randomized (1:1) to subcutaneous mepolizumab (300 mg) or placebo every 4 weeks for 32weeks, plus existing HES therapy. The primary outcome was the proportion of patients with 1 or more flares (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 end points were also assessed. The proportion of patients experiencing 1 or more flares/withdrawing from the study was 50% lower with mepolizumab versus placebo (15 of 54 [28%] vs 30 of 54 [56%]; P = .002). Logistic regression analysis was consistent with the primary analysis (odds ratio, 0.28; 95% CI, 0.12–0.64; P = .003). Similar proportions of patients in the mepolizumab and placebo groups experienced on-treatment adverse events (48 of 54 [89%] vs 47 of 54 [87%]). Compared with placebo, mepolizumab significantly reduced the occurrence of flares in patients with HES, with no new safety signals identified.
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影响因子：
14.2
作者：
Garrett, JK;Jameson, SC;Rothenberg, ME
通讯作者：
Rothenberg, ME
影响因子：
14.2
作者：
Stein, Miguel L.;Villanueva, Joyce M.;Rothenberg, Marc E.
通讯作者：
Rothenberg, Marc E.
影响因子：
158.5
作者：
Rothenberg, Marc E.;Klion, Amy D.;Gleich, Gerald J.
通讯作者：
Gleich, Gerald J.
影响因子：
14.2
作者：
Ogbogu, Princess U.;Bochner, Bruce S.;Butterfield, Joseph H.;Gleich, Gerald J.;Huss-Marp, Johannes;Kahn, Jean Emmanuel;Leiferman, Kristin M.;Nutman, Thomas B.;Pfab, Florian;Ring, Johannes;Rothenberg, Marc E.;Roufosse, Florence;Sajous, Marie-Helene;Sheikh, Javed;Simon, Dagmar;Simon, Hans-Uwe;Stein, Miguel L.;Wardlaw, Andrew;Weller, Peter F.;Klion, Amy D.
通讯作者：
Klion, Amy D.
影响因子：
158.5
作者：
Plotz, S;Simon, H;Ring, J
通讯作者：
Ring, J