Treatment of patients with the hypereosinophilic syndrome with mepolizumab
Treatment of patients with the hypereosinophilic syndrome with mepolizumab
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DOI：
10.1056/nejmoa070812
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发表时间：
2008-03-20
影响因子：
158.5
通讯作者：
Gleich, Gerald J.
中科院分区：
文献类型：
--
作者：
Rothenberg, Marc E.;Klion, Amy D.;Gleich, Gerald J.
背景：嗜酸性粒细胞增多综合征是一组以持续性血液嗜酸性粒细胞增多为特征的疾病，定义为每微升超过 1500 个细胞，伴有终末器官受累且无公认的继发原因。虽然大多数患者对皮质类固醇有反应，但副作用很常见，并可能导致相当大的发病率。方法：我们进行了一项国际、随机、双盲、安慰剂对照试验，评估抗白细胞介素 5 单克隆抗体美泊利单抗 (mepolizumab) 在嗜酸性粒细胞增多综合征患者中的安全性和有效性。患者的FIP1L1-PDGFRA融合基因呈阴性，需要泼尼松单药治疗，每天20至60毫克，以维持稳定的临床状态和血液嗜酸性粒细胞计数低于1000/微升。患者接受静脉注射美泊利单抗或安慰剂，同时逐渐减少泼尼松剂量。主要终点是将强的松剂量减少至每天 10 mg 或更少，持续 8 周或以上。 结果：美泊利单抗组 84% 的患者达到主要终点，而安慰剂组只有 43% 的患者达到主要终点（风险比，2.90；95% 置信区间 [CI]，1.59 至 5.26；P
Background: The hypereosinophilic syndrome is a group of diseases characterized by persistent blood eosinophilia, defined as more than 1500 cells per microliter with end-organ involvement and no recognized secondary cause. Although most patients have a response to corticosteroids, side effects are common and can lead to considerable morbidity.Methods: We conducted an international, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of an anti-interleukin-5 monoclonal antibody, mepolizumab, in patients with the hypereosinophilic syndrome. Patients were negative for the FIP1L1-PDGFRA fusion gene and required prednisone monotherapy, 20 to 60 mg per day, to maintain a stable clinical status and a blood eosinophil count of less than 1000 per microliter. Patients received either intravenous mepolizumab or placebo while the prednisone dose was tapered. The primary end point was the reduction of the prednisone dose to 10 mg or less per day for 8 or more consecutive weeks.Results: The primary end point was reached in 84% of patients in the mepolizumab group, as compared with 43% of patients in the placebo group (hazard ratio, 2.90; 95% confidence interval [CI], 1.59 to 5.26; P