Poullin P, Bornet C, Veyradier A, Coppo P
Service d'Hémaphérèse, Hôpital de La Conception, Marseille, France; Centre de Référence des Microangiopathies Thrombotiques, Paris, France.
Pharmacie Usage Intérieur, Hôpital de la Conception, Marseille, France.
Drugs Today (Barc). 2019 Jun;55(6):367-376. doi: 10.1358/dot.2019.55.6.2989843.
Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening disease characterized by microangiopathic hemolytic anemia, thrombocytopenia and multiorgan failure, resulting from autoantibody-mediated severe A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) deficiency. In spite of treatment with plasma exchange and immunosuppression, patients remain at risk of exacerbations, refractoriness and death. Caplacizumab (Cablivi; Ablynx, a Sanofi company), a nanobody targeting von Willebrand factor (vWF), has been recently approved in the E.U. and the U.S. as the first therapeutic specifically indicated for the treatment of adults experiencing an episode of iTTP. Caplacizumab blocks the interaction of all multimers with platelets and, therefore, has an immediate effect on platelet aggregation and the ensuing formation and accumulation of platelet-rich microthrombi. This immediate effect of caplacizumab has the potential to protect the patient from tissue ischemia and organ dysfunction while the underlying disease process resolves. We detail here the preclinical and clinical data on caplacizumab for iTTP, including the recent studies that led to approval by the U.S. Food and Drug Administration (FDA) in 2019.
免疫介导的血栓性血小板减少性紫癜（iTTP）是一种罕见且危及生命的疾病，其特征为微血管病性溶血性贫血、血小板减少和多器官功能衰竭，由自身抗体介导的具有血小板反应蛋白基序的解聚素和金属蛋白酶13（ADAMTS13）严重缺乏所致。尽管采用了血浆置换和免疫抑制治疗，但患者仍有病情加重、难治和死亡的风险。卡泊单抗（Cablivi；阿柏利斯公司，赛诺菲旗下）是一种靶向血管性血友病因子（vWF）的纳米抗体，最近已在欧盟和美国获批，成为首个专门用于治疗成人iTTP发作的疗法。卡泊单抗可阻断所有多聚体与血小板的相互作用，因此对血小板聚集以及随后富含血小板的微血栓的形成和积聚具有即刻作用。在潜在疾病进程得到解决的同时，卡泊单抗的这种即刻作用有可能保护患者免受组织缺血和器官功能障碍的影响。我们在此详细介绍卡泊单抗治疗iTTP的临床前和临床数据，包括导致其于2019年获得美国食品药品监督管理局（FDA）批准的近期研究。
