Department of Paediatrics, Haematology and Oncology, Medical University of Warsaw, Warsaw, Poland.
Motol University Hospital, Prague, Czech Republic.
Haemophilia. 2018 Mar;24(2):221-228. doi: 10.1111/hae.13385. Epub 2018 Jan 3.
Octanate is a human, plasma-derived, von Willebrand factor-stabilized coagulation factor VIII (FVIII) concentrate with demonstrated haemostatic efficacy in previously treated patients with haemophilia A.
This prospective, open-label study aimed to assess the immunogenicity of octanate in previously untreated patients (PUPs).
The study monitored development of FVIII inhibitors in 51 PUPs. Tolerability, viral safety, FVIII recovery and efficacy of octanate for the prevention and treatment of bleeds and in surgical procedures were also assessed.
Five (9.8%) of the 51 patients developed inhibitors during the study, 4 of which (7.8%) were high titre. Three inhibitor cases (5.9%) were considered clinically relevant; 2 were transient inhibitors that disappeared during regular octanate treatment without a change in dose or treatment frequency. Amongst 45 patients with FVIII:C <1% at baseline and who received ≥20 exposure days (EDs) or had <20 EDs but developed an inhibitor, inhibitor incidence was 11.1% (6.7% clinically relevant). All clinically relevant inhibitors developed within 20 EDs of on-demand treatment. No inhibitors developed in PUPs receiving prophylaxis. All patients who developed inhibitors had either intron 22 inversions or large deletions. Irrespective of the reason for administration, haemostatic efficacy was rated as "excellent" in 99.6% of all infusions (4700 of 4717 infusions), and no complications were reported in 23 surgical procedures. Mean incremental in vivo recovery was 2.0%/IU/kg (±0.7) and 1.9%/IU/kg (±0.5) for the first and second assessments, respectively. Tolerability was rated "very good" in 99.9% of infusions.
In PUPs with severe haemophilia A, octanate demonstrated haemostatic efficacy with a low rate of inhibitor development.
辛酸盐是一种人血浆来源的、经 von Willebrand 因子稳定的凝血因子 VIII（FVIII）浓缩物，在既往接受过治疗的血友病 A 患者中已显示出止血疗效。
本前瞻性、开放性研究旨在评估辛酸盐在既往未接受过治疗的患者（PUP）中的免疫原性。
该研究监测了 51 例 PUP 中 FVIII 抑制剂的发展情况。还评估了辛酸盐的耐受性、病毒安全性、FVIII 回收率以及预防和治疗出血和手术过程中的疗效。
在研究期间，51 例患者中有 5 例（9.8%）产生了抑制剂，其中 4 例（7.8%）为高滴度。3 例抑制剂病例（5.9%）被认为具有临床相关性；2 例为短暂抑制剂，在常规辛酸盐治疗期间消失，而无需改变剂量或治疗频率。在基线 FVIII：C <1%且接受了≥20 个暴露日（ED）或接受了<20 ED 但产生了抑制剂的 45 例患者中，抑制剂发生率为 11.1%（6.7%具有临床相关性）。所有具有临床相关性的抑制剂均在按需治疗的 20 ED 内产生。接受预防治疗的 PUP 未产生抑制剂。所有产生抑制剂的患者均存在内含子 22 倒位或大片段缺失。无论给药原因如何，所有输注的止血疗效均被评为“优秀”（4717 次输注中的 4700 次），23 例手术中未报告任何并发症。首次和第二次评估的平均体内增量恢复分别为 2.0%/IU/kg（±0.7）和 1.9%/IU/kg（±0.5）。99.9%的输注被评为“非常好”。
在重度血友病 A 的 PUP 中，辛酸盐表现出止血疗效，抑制剂的发生率较低。
