Austin S K, Kavakli K, Norton M, Peyvandi F, Shapiro A
St. George's Haemophilia Centre, St. George's University Hospitals NHS Foundation Trust, London, UK.
Department of Pediatric Hematology, Children's Hospital, Ege University Faculty of Medicine, Izmir, Turkey.
Haemophilia. 2016 May;22(3):419-25. doi: 10.1111/hae.12893. Epub 2016 Mar 8.
Hereditary factor X (FX) deficiency is a rare bleeding disorder affecting 1:500 000 to 1:1 000 000 of individuals. Until recently, no specific replacement factor concentrate was available.
The aim of this study was to assess safety and efficacy of a new, high-purity plasma-derived FX concentrate (pdFX) in subjects with hereditary FX deficiency.
Subjects aged ≥12 years with moderate or severe FX deficiency (plasma FX activity <5 IU dL(-1) ) received 25 IU kg(-1) pdFX as on-demand treatment or short-term prophylaxis for 6 months to 2 years. Subjects assessed pdFX efficacy for each bleed; at end-of-study, investigators assessed overall pdFX efficacy. Blood samples for pharmacokinetic analysis were obtained at baseline and ≥6 months. Safety was assessed by adverse events (AEs), inhibitor development and changes in laboratory parameters.
Sixteen enrolled subjects (six aged 12-17 years; 10 aged 18-58 years) received a total of 468 pdFX infusions. In the 187 analysed bleeds, pdFX efficacy was categorized as excellent, good, poor or unassessable in 90.9%, 7.5%, 1.1% and 0.5% of bleeds respectively; 83% of bleeds were treated with one infusion. For pdFX, mean (median; interquartile range) incremental recovery and half-life were 2.00 (2.12; 1.79-2.37) IU dL(-1) per IU kg(-1) and 29.4 (28.6; 25.8-33.1) h respectively. No serious AEs possibly related to pdFX or evidence of FX inhibitors were observed, and no hypersensitivity reactions or clinically significant trends were detected in laboratory parameters.
These results demonstrate that a dose of 25 IU kg(-1) pdFX is safe and efficacious for on-demand treatment and short-term prophylaxis in subjects with moderate or severe hereditary FX deficiency.
遗传性因子X（FX）缺乏症是一种罕见的出血性疾病，发病率为1/500000至1/1000000。直到最近，还没有可用的特异性替代因子浓缩物。
本研究旨在评估一种新型高纯度血浆源性FX浓缩物（pdFX）在遗传性FX缺乏症患者中的安全性和有效性。
年龄≥12岁、患有中度或重度FX缺乏症（血浆FX活性<5 IU dL⁻¹）的受试者接受25 IU kg⁻¹的pdFX按需治疗或短期预防，为期6个月至2年。受试者评估每次出血时pdFX的疗效；在研究结束时，研究人员评估pdFX的总体疗效。在基线和≥6个月时采集血样进行药代动力学分析。通过不良事件（AE）、抑制剂产生情况和实验室参数变化评估安全性。
16名入组受试者（6名年龄在
12 - 17岁；10名年龄在18 - 58岁）共接受了468次pdFX输注。在187次分析的出血事件中，pdFX疗效分别被分类为极佳、良好、较差或不可评估的比例为90.9%、7.5%、1.1%和0.5%；83%的出血事件通过一次输注进行治疗。对于pdFX，平均（中位数；四分位间距）增量回收率和半衰期分别为每IU kg⁻¹ 2.00（2.12；1.79 - 2.37）IU dL⁻¹和29.4（28.6；25.8 - 33.1）小时。未观察到可能与pdFX相关的严重AE或FX抑制剂的证据，并且在实验室参数中未检测到过敏反应或具有临床意义的趋势。
这些结果表明，25 IU kg⁻¹的pdFX剂量对于中度或重度遗传性FX缺乏症患者的按需治疗和短期预防是安全有效的。
