Terminal Complement Inhibitor Eculizumab in Atypical Hemolytic-Uremic Syndrome
Terminal Complement Inhibitor Eculizumab in Atypical Hemolytic-Uremic Syndrome
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DOI：
10.1056/nejmoa1208981
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发表时间：
2013-06-06
影响因子：
158.5
通讯作者：
Loirat, C.
中科院分区：
文献类型：
--
作者：
Legendre, C. M.;Licht, C.;Loirat, C.
非典型溶血性尿毒症综合征是一种遗传性、危及生命的补体介导的血栓性微血管病。血浆置换或输液可能暂时维持正常水平的血液学措施，但不治疗潜在的全身性diseases.MethodsWe进行了两个前瞻性的2期试验中，非典型溶血性尿毒症综合征的患者谁是12岁或以上，接受依库珠单抗26周，并在长期扩展阶段。招募了血小板计数低且肾损害的患者（试验1）和血浆置换或输注期间血小板计数至少8周未下降超过25%的肾损害患者（试验2）。主要终点包括血小板计数的变化（在试验1中）和血栓性微血管病无事件状态（血小板计数没有减少> 25%，没有血浆交换或输注，没有开始透析）（在试验2中）。依库珠单抗导致血小板计数增加;在试验1中，从基线到第26周，血小板计数平均增加73 × 109/L（P
BackgroundAtypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease.MethodsWe conducted two prospective phase 2 trials in which patients with atypical hemolytic-uremic syndrome who were 12 years of age or older received eculizumab for 26 weeks and during long-term extension phases. Patients with low platelet counts and renal damage (in trial 1) and those with renal damage but no decrease in the platelet count of more than 25% for at least 8 weeks during plasma exchange or infusion (in trial 2) were recruited. The primary end points included a change in the platelet count (in trial 1) and thrombotic microangiopathy event-free status (no decrease in the platelet count of >25%, no plasma exchange or infusion, and no initiation of dialysis) (in trial 2).ResultsA total of 37 patients (17 in trial 1 and 20 in trial 2) received eculizumab for a median of 64 and 62 weeks, respectively. Eculizumab resulted in increases in the platelet count; in trial 1, the mean increase in the count from baseline to week 26 was 73x10(9) per liter (P