Prezotti Alessandra N L, Frade-Guanaes Jéssica O, Yamaguti-Hayakawa Gabriela G, Ozelo Margareth C
Department of Internal Medicine, School of Medical Sciences, University of Campinas, UNICAMP, Rua Tessália Vieira de Camargo, 126, Cidade Universitária, Campinas 13083-887, SP, Brazil.
HEMOES, Hematology and Hemotherapy Center Dr. Marcos Daniel Santos, Av. Marechal Campos, 1468, Maruípe, Vitória 29047-105, ES, Brazil.
Pharmaceuticals (Basel). 2022 Jul 23;15(8):911. doi: 10.3390/ph15080911.
Anti-drug antibody (ADA) development is a significant complication in the treatment of several conditions. For decades, the mainstay of hemophilia A treatment was the replacement of deficient coagulation factor VIII (FVIII) to restore hemostasis, control, and prevent bleeding events. Recently, new products have emerged for hemophilia A replacement therapy, including bioengineered FVIII molecules with enhanced pharmacokinetic profiles: the extended half-life (EHL) recombinant FVIII products. However, the main complication resulting from replacement treatment in hemophilia A is the development of anti-FVIII neutralizing alloantibodies, known as inhibitors, affecting approximately 25-30% of severe hemophilia A patients. Therefore, the immunogenicity of each FVIII product and the mechanisms that could help increase the tolerance to these products have become important research topics in hemophilia A. Furthermore, patients with inhibitors continue to require effective treatment for breakthrough bleedings and procedures, despite the availability of non-replacement therapy, such as emicizumab. Herein, we discuss the currently licensed treatments available for hemophilia A and the immunogenicity of new therapies, such as EHL-rFVIII products, compared to other products available.
抗药物抗体（ADA）的产生是多种疾病治疗中的一个重大并发症。几十年来，甲型血友病治疗的主要方法是补充缺乏的凝血因子VIII（FVIII），以恢复止血功能、控制并预防出血事件。最近，出现了用于甲型血友病替代疗法的新产品，包括具有改善药代动力学特征的生物工程FVIII分子：延长半衰期（EHL）重组FVIII产品。然而，甲型血友病替代治疗产生的主要并发症是抗FVIII中和性同种抗体（即抑制剂）的产生，约25%-30%的重度甲型血友病患者会受到影响。因此，每种FVIII产品的免疫原性以及有助于提高对这些产品耐受性的机制，已成为甲型血友病研究的重要课题。此外，尽管有非替代疗法（如艾美赛珠单抗），但有抑制剂的患者在发生突破性出血和进行手术时仍需要有效的治疗。在此，我们讨论目前已获许可用于甲型血友病的治疗方法，以及与其他可用产品相比，新疗法（如EHL-rFVIII产品）的免疫原性。
