Shapiro Amy D
Indiana Hemophilia and Thrombosis Center, 8402 Harcourt Rd, Suite 420, Indianapolis, IN 46260 USA.
Vasc Health Risk Manag. 2007;3(5):555-65.
Removal of blood-based additives from recombinant clotting factor concentrates continues to be advocated by the hemophilia community due to the history of infectious disease transmission with previous blood-derived clotting factor concentrates. In 2003, octocog-alpha, antihemophilic factor (recombinant), plasma/albumin-free method (ADVATE) was introduced, providing the first third-generation recombinant factor VIII (rFVIII) concentrate. Completed clinical trials have demonstrated ADVATE to be safe and effective in adult and pediatric subjects utilizing both prophylactic and on-demand treatment regimens, and for perioperative hemostatic coverage. In the five completed studies involving more than 200 previously treated patients (PTPs), a single incidence of low-titer, non-persistent inhibitor was reported. Active post authorization safety surveillance (PASS) is being performed to expand the efficacy and safety profile of ADVATE in routine clinical practice. Laboratory studies have documented the storage and post-reconstitution stability of ADVATE, conferring the desired versatility for home treatment. The evolving real-world experience and ongoing studies will provide further insight into ADVATE pharmacokinetics, alternative prophylactic dosing regimens, methods for perioperative hemostatic management, and utility in immune tolerance induction. Experience with ADVATE, and its place in today's treatment paradigm, is the focus of this article.
由于既往血液源性凝血因子浓缩物存在传染病传播史，血友病群体仍主张从重组凝血因子浓缩物中去除血液源性添加剂。2003年，八因子重组抗血友病因子（重组）无血浆/白蛋白方法（ADVATE）问世，成为首个第三代重组凝血因子VIII（rFVIII）浓缩物。已完成的临床试验表明，ADVATE在成人和儿童患者中采用预防和按需治疗方案以及围手术期止血覆盖方面均安全有效。在五项涉及200多名既往治疗患者（PTP）的已完成研究中，报告了一例低滴度、非持续性抑制剂的单一病例。正在进行主动上市后安全性监测（PASS），以扩大ADVATE在常规临床实践中的疗效和安全性。实验室研究记录了ADVATE的储存和复溶后稳定性，使其具有家庭治疗所需的多功能性。不断发展的真实世界经验和正在进行的研究将进一步深入了解ADVATE的药代动力学、替代预防给药方案、围手术期止血管理方法以及免疫耐受诱导中的效用。ADVATE的经验及其在当今治疗模式中的地位是本文的重点。
