Long-acting recombinant factor VIII Fc fusion protein (rFVIIIFc) for perioperative haemostatic management in severe haemophilia A
Long-acting recombinant factor VIII Fc fusion protein (rFVIIIFc) for perioperative haemostatic management in severe haemophilia A
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DOI：
10.1160/th15-10-0780
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发表时间：
2016-07-01
影响因子：
6.7
通讯作者：
Robinson, Brian
中科院分区：
文献类型：
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作者：
Mahlangu, Johnny N.;Ragni, Margaret;Robinson, Brian
III期A-LONG和Kids A-LONG研究证明了rFVIIIFc的半衰期较rFVIII延长，以及rFVIIIFc在重度血友病A受试者中的安全性和疗效。来自A-LONG和Kids A-LONG的合格受试者通过入组ASPIRE（一项正在进行的扩展研究）继续rFVIIIFc治疗。基于主要研究的合并数据和ASPIRE中期数据，评价了rFVIIIFc在需要手术的受试者中的安全性和疗效。围手术期给药方案由研究者根据药代动力学数据和临床给药委员会的建议确定。除给药频率外，还评估了因子消耗、失血量、输血、出血事件和止血反应。在各项研究中，21例受试者接受了23次可评价的大手术，包括19次骨科手术; 41例受试者接受了52次小手术，包括30次牙科手术。在儿科受试者中未进行大手术，进行了10次小手术。在评估止血反应的大手术（n = 22）和小手术（n = 32）中，所有手术均被研究者/外科医生评定为极好或良好。在大多数大手术期间（95.7%），通过1次rFVIIIFc输注维持止血。大手术中的失血量与非血友病受试者中的类似手术一致。在各项研究中，rFVIIIFc的耐受性良好;无受试者产生抑制剂。
The Phase 3 A-LONG and Kids A-LONG studies demonstrated the prolonged half-life of rFVIIIFc compared with rFVIII, and the safety and efficacy of rFVIIIFc in subjects with severe haemophilia A. Eligible subjects from A-LONG and Kids A-LONG continued rFVIIIFc treatment by enrolling in ASPIRE, an ongoing extension study. Based on combined data from the primary studies and ASPIRE interim data, the safety and efficacy of rFVIIIFc in subjects requiring surgery were evaluated. Perioperative dosing regimens were determined by investigators with guidance based on pharmacokinetic data and recommendations from a clinical dosing committee. In addition to dosing frequency, factor consumption, blood loss, transfusions, bleeding episodes, and haemostatic response were assessed. Across studies, 21 subjects underwent 23 evaluable major surgeries, including 19 orthopaedic surgeries; 41 subjects underwent 52 minor surgeries, including 30 dental procedures. No major and 10 minor surgeries were performed in paediatric subjects. Of the major (n = 22) and minor (n = 32) surgeries assessed for haemostatic response, all were rated as excellent or good by the investigator/surgeon. During most major surgeries (95.7 %), haemostasis was maintained with one rFVIIIFc infusion. Blood loss in major surgeries was consistent with similar surgeries in subjects without haemophilia. Across studies, rFVIIIFc was well tolerated; no subject developed an inhibitor.