Hospital Universitario La Paz, Unidad de Coagulopatías, Servicio de Hematología, Autonoma University, Madrid, Spain.
Klinikum Bremen-Mitte, Professor Hess Children's Hospital, Bremen, Germany.
Haemophilia. 2021 May;27(3):340-350. doi: 10.1111/hae.14167. Epub 2021 Mar 20.
New therapeutic agents for haemophilia with inhibitors that are in development or already licensed are expected to provide transformative treatment options. Many of these new therapies are not based on simply replacing the missing factor; new strategies include bispecific antibody technology that mimics factor VIII coagulation function (emicizumab), and inhibition of anticoagulant proteins such as tissue factor pathway inhibitor (eg PF-06741086) and antithrombin (eg fitusiran). These agents are administered subcutaneously and should significantly reduce treatment burden and increase the ability to deliver prophylaxis for patients. Limited real-world data and validated practical guidance on these recently licensed/upcoming treatments resulted in the authors convening to discuss recommendations on their use. Emicizumab is currently the only licenced nonfactor therapy; thus, our recommendations focus on this product. Target candidates for emicizumab prophylaxis are difficult-to-treat patients with haemophilia A and inhibitors and/or venous access issues, frequent bleeds and target joints. In case of breakthrough bleeding while receiving emicizumab, patients still require treatment with bypassing agents; the adjunct treatment of choice is recombinant activated factor VII. This treatment is also recommended to prevent bleeds in patients with inhibitors undergoing surgery. Our recommendations on suitable laboratory assays and monitoring new products, as well as the benefit of patient-reported outcomes (such as pain and physical activity levels), are included. We also briefly discuss future treatment options for patients with haemophilia B and inhibitors. Although these nonfactor treatments offer great promise, further data and real-world evidence are needed.
正在开发或已经获得许可的针对有抑制剂的血友病的新型治疗药物有望提供变革性的治疗选择。这些新疗法中的许多并非简单地替代缺失的因子；新策略包括模拟因子 VIII 凝血功能的双特异性抗体技术（emicizumab），以及抑制抗凝蛋白，如组织因子途径抑制剂（如 PF-06741086）和抗凝血酶（如 fitusiran）。这些药物通过皮下给药，应能显著降低治疗负担并提高预防治疗的能力。由于这些最近获得许可/即将推出的治疗方法的实际数据有限且缺乏经过验证的实用指南，作者们召集在一起讨论了关于其使用的建议。Emicizumab 是目前唯一获得许可的非因子治疗药物；因此，我们的建议主要集中在该产品上。Emicizumab 预防治疗的候选目标是难以治疗的血友病 A 患者和有抑制剂和/或静脉通路问题、频繁出血和目标关节的患者。在接受 Emicizumab 治疗时发生突破性出血的情况下，患者仍需要使用旁路药物治疗；首选的辅助治疗是重组激活因子 VII。该治疗方法也建议用于预防接受手术治疗的有抑制剂的患者出血。我们还包括了关于适合的实验室检测和监测新产品的建议，以及患者报告的结果（如疼痛和身体活动水平）的益处。我们还简要讨论了血友病 B 和抑制剂患者的未来治疗选择。尽管这些非因子治疗方法有很大的前景，但仍需要更多的数据和真实世界的证据。
