Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura
Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura
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DOI：
10.1056/nejmoa1806311
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发表时间：
2019-01-24
影响因子：
158.5
通讯作者：
Zeldin, R. K.
中科院分区：
文献类型：
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作者：
Scully, M.;Cataland, S. R.;Zeldin, R. K.
背景在获得性血栓性血小板减少性紫癜（TTP）中，免疫介导的血管性血友病因子裂解蛋白酶ADAMTS 13的缺陷允许血管性血友病因子多聚体不受限制地粘附于血小板和微血栓形成，这导致血小板减少症、溶血性贫血和组织缺血。Caplacizumab，抗血管性血友病因子人源化，二价可变域的唯一免疫球蛋白片段，抑制血管性血友病因子多聚体和platelets. METHODS之间的相互作用在这个双盲，对照试验，我们随机分配145例TTP接受caplacizumab（10毫克静脉负荷丸，然后10毫克每天皮下注射）或安慰剂在血浆置换和此后30天。主要结局是血小板计数恢复正常的时间，此后5天内停止每日血浆置换。关键次要结局包括试验治疗期间TTP相关死亡、TTP复发或血栓栓塞事件的复合终点;试验期间任何时间TTP复发;难治性TTP; caplacizumab组血小板计数恢复正常的中位时间短于安慰剂组，（2.69天[95%置信区间{CI}，1.89至2.83] vs. 2.88天[95% CI，2.68至3.56]，P = 0.01），接受caplacizumab治疗的患者血小板计数正常化的可能性是接受安慰剂治疗患者的1.55倍。caplacizumab组发生复合结局事件的患者百分比比安慰剂组低74%（12% vs. 49%，P
BACKGROUNDIn acquired thrombotic thrombocytopenic purpura (TTP), an immune-mediated deficiency of the von Willebrand factor-cleaving protease ADAMTS13 allows unrestrained adhesion of von Willebrand factor multimers to platelets and microthrombosis, which result in thrombocytopenia, hemolytic anemia, and tissue ischemia. Caplacizumab, an anti-von Willebrand factor humanized, bivalent variable-domain-only immunoglobulin fragment, inhibits interaction between von Willebrand factor multimers and platelets.METHODSIn this double-blind, controlled trial, we randomly assigned 145 patients with TTP to receive caplacizumab (10-mg intravenous loading bolus, followed by 10 mg daily subcutaneously) or placebo during plasma exchange and for 30 days thereafter. The primary outcome was the time to normalization of the platelet count, with discontinuation of daily plasma exchange within 5 days thereafter. Key secondary outcomes included a composite of TTP-related death, recurrence of TTP, or a thromboembolic event during the trial treatment period; recurrence of TTP at any time during the trial; refractory TTP; and normalization of organ-damage markers.RESULTSThe median time to normalization of the platelet count was shorter with caplacizumab than with placebo (2.69 days [95% confidence interval {CI}, 1.89 to 2.83] vs. 2.88 days [95% CI, 2.68 to 3.56], P = 0.01), and patients who received caplacizumab were 1.55 times as likely to have a normalization of the platelet count as those who received placebo. The percentage of patients with a composite outcome event was 74% lower with caplacizumab than with placebo (12% vs. 49%, P