Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency
Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency
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DOI：
10.1111/hae.12893
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发表时间：
2016-05-01
期刊：
影响因子：
3.9
通讯作者：
Shapiro, A.
中科院分区：
文献类型：
--
作者：
Austin, S. K.;Kavakli, K.;Shapiro, A.
遗传性因子X（FX）缺乏症是一种罕见的出血性疾病，影响1：500 000至1：1 000 000的个体。直到最近，还没有特定的替代因子浓缩物可用。目的：本研究的目的是评估一种新的高纯度血浆衍生FX浓缩物（pdFX）在遗传性FX缺乏症受试者中的安全性和有效性。方法：受试者年龄≥ 12岁，中度或重度FX缺乏（血浆FX活性= 6个月）。通过不良事件（AE）、抑制物产生和实验室参数变化评估安全性。结果：16例入组受试者（6例年龄为12-17岁; 10例年龄为18-58岁）共接受了468次pdFX输注。在分析的187例出血中，分别有90.9%、7.5%、1.1%和0.5%的出血的pdFX疗效被分类为极好、良好、差或无法评估; 83%的出血通过一次输注治疗。对于pdFX，平均值（中位数;四分位距）增量回收率和半衰期分别为2.00（2.12; 1.79-2.37）IU dL（-1）/IU kg（-1）和29.4（28.6; 25.8-33.1）h。未观察到可能与pdFX相关的严重AE或FX抑制剂的证据，在实验室参数中未检测到超敏反应或具有临床意义的趋势。结论：这些结果表明，对于中度或重度遗传性FX缺乏症受试者，25 IU kg（-1）pdFX的按需治疗和短期预防是安全有效的。
Introduction: 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. Aim: 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. Methods: Subjects aged >= 12 years with moderate or severe FX deficiency (plasma FX activity = 6 months. Safety was assessed by adverse events (AEs), inhibitor development and changes in laboratory parameters. Results: 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. Conclusion: 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.