Centre National de Référence des MicroAngiopathies Thrombotiques, Paris, France.
Service d'hématologie biologique, Hôpital Lariboisière, Assistance Publique - Hôpitaux de Paris, Paris, France.
J Thromb Haemost. 2021 Jan;19(1):58-67. doi: 10.1111/jth.15194. Epub 2020 Dec 17.
Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening disease that causes systemic platelet-rich microthrombi with multiorgan damage. The historical treatment is based on therapeutic plasma exchange (TPE) and immunosuppression. Despite survival rates exceeding 85%, unfavorable outcomes including refractoriness, death, and exacerbations of the disease during treatment still calls for a better management strategy. Caplacizumab (Cablivi) appeared recently as a new treatment in iTTP. By inhibiting binding of von Willebrand factor to platelets, caplacizumab prevents platelets aggregation and the formation of microthrombi. Two pivotal randomized controlled trials have provided positive results where the use of caplacizumab is associated with faster platelet count recovery and less unfavorable outcomes. The other strength of this agent is an impressive alleviation in the burden of care, consisting in less TPE sessions and lower volumes of plasma to achieve remission, as well as substantial shortening in the length of hospitalization. However, since the recent approval of caplacizumab for the treatment of iTTP on the basis of these studies, debates remain regarding its systematic use in this indication. Should all patients be benefited from caplacizumab? Should we reserve caplacizumab only to the more severe patients? Should caplacizumab be initiated frontline or as a salvage therapy? If applicable, how should we select patients for caplacizumab? Last, is caplacizumab treatment cost-effective? This review aims at addressing these specific questions at a time when iTTP is entering the area of targeted therapies.
免疫介导性血栓性血小板减少性紫癜（iTTP）是一种罕见的、危及生命的疾病，可导致全身血小板丰富的微血栓形成，并伴有多器官损伤。历史上的治疗方法基于治疗性血浆置换（TPE）和免疫抑制。尽管生存率超过 85%，但仍存在不良结局，包括难治性、死亡和治疗期间疾病恶化，这仍然需要更好的管理策略。卡普雷珠单抗（Cablivi）最近作为 iTTP 的一种新治疗方法出现。通过抑制血管性血友病因子与血小板的结合，卡普雷珠单抗可防止血小板聚集和微血栓形成。两项关键性随机对照试验均取得了积极结果，表明卡普雷珠单抗的使用与更快的血小板计数恢复和更少的不良结局相关。该药物的另一个优势是显著减轻了护理负担，包括减少 TPE 治疗次数和血浆用量以达到缓解，以及显著缩短住院时间。然而，自从卡普雷珠单抗基于这些研究被批准用于治疗 iTTP 以来，关于其在该适应证中的系统使用仍存在争议。所有患者都应受益于卡普雷珠单抗吗？我们是否应该仅将卡普雷珠单抗保留给更严重的患者？卡普雷珠单抗应该作为一线治疗还是挽救治疗？如果适用，我们应该如何选择卡普雷珠单抗的患者？最后，卡普雷珠单抗治疗是否具有成本效益？当 iTTP 进入靶向治疗领域时，本综述旨在回答这些具体问题。
