Beyond plasma exchange: novel therapies for thrombotic thrombocytopenic purpura
Beyond plasma exchange: novel therapies for thrombotic thrombocytopenic purpura
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DOI：
10.1182/asheducation-2018.1.539
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发表时间：
2018-11-01
影响因子：
3
通讯作者：
Chaturvedi, Shruti
中科院分区：
文献类型：
--
作者：
Dane, Kathryn;Chaturvedi, Shruti
血浆置换的出现极大地改变了急性血栓性血小板减少性紫癜（TTP）的预后。最近对TTP发病机制的深入了解导致了针对致病性抗ADAMTS 13抗体产生、血管性血友病因子（VWF）-血小板相互作用和ADAMTS 13替代的新型疗法的开发。回顾性和前瞻性研究已经确定了利妥昔单抗作为急性TTP患者血浆置换的辅助治疗的疗效，无论是前期还是难治性疾病。复发预防是急性UP幸存者的主要关注点，新出现的数据支持利妥昔单抗在持续或复发性ADAMTS 13缺乏症临床缓解患者中的预防性使用。Capalcizumab是一种针对VWF结构域A1的纳米抗体，可防止VWF-血小板聚集体的形成，最近完成了2期（TITAN）和3期（HERCULES）试验，结果令人鼓舞。与安慰剂相比，caplacizumab缩短了血小板恢复的时间，并可防止TTP急性期的微血栓形成组织损伤，尽管它不会改变潜在的免疫应答。其他有希望的治疗方法包括浆细胞抑制剂（硼替佐米）、重组ADAMTS 13、N-乙酰半胱氨酸和VWF-糖蛋白Ib/IX相互作用抑制剂（安非巴肽）正在开发中，其中几种药物正在进行前瞻性临床研究，以评估其在TTP中的疗效和作用。在未来几年，我们乐观地认为，新的治疗方法和国际合作努力将带来更有效的，以证据为基础的方法来解决难治性急性TTP和复发预防。
The advent of plasma exchange has dramatically changed the prognosis of acute thrombotic thrombocytopenic purpura (TTP). Recent insights into TTP pathogenesis have led to the development of novel therapies targeting pathogenic anti-ADAMTS13 antibody production, von Willebrand factor (VWF)-platelet interactions, and ADAMTS13 replacement Retrospective and prospective studies have established the efficacy of rituximab as an adjunct to plasma exchange for patients with acute TTP, either upfront or for refractory disease. Relapse prevention is a major concern for survivors of acute UP, and emerging data support the prophylactic use of rituximab in patients with persistent or recurrent ADAMTS13 deficiency in clinical remission. Capalcizumab, a nanobody directed against domain A1 of VWF that prevents the formation of VWF-platelet aggregates, recently completed phase 2 (TITAN) and 3 (HERCULES) trials with encouraging results. Compared with placebo, caplacizumab shortened the time to platelet recovery and may protect against microthrombotic tissue injury in the acute phase of TTP, though it does not modify the underlying immune response. Other promising therapies including plasma cell inhibitors (bortezomib), recombinant ADAMTS13, N-acetyl cysteine, and inhibitors of the VWF-glycoprotein Ib/IX interaction (anfibatide) are in development, and several of these agents are in prospective clinical studies to evaluate their efficacy and role in TTP. In the coming years, we are optimistic that novel therapies and international collaborative efforts will usher in even more effective, evidence-based approaches to address refractory acute TTP and relapse prevention.