Lambert Thierry, Rothschild Chantal, Volot Fabienne, Borel-Derlon Annie, Trossaërt Marc, Claeyssens-Donadel Ségolène, Attal Sepideh
Haemophilia Care Centre, Bicêtre APHP University Hospital, Le Kremlin, Bicêtre, France.
Haemophilia Care Centre, Department of Haematology, Necker APHP University Hospital, Paris, France.
Transfusion. 2017 Apr;57(4):1066-1071. doi: 10.1111/trf.13988. Epub 2017 Mar 24.
Nonacog alfa, the recombinant Factor IX (F IX) used for the treatment of hemophilia B, was approved in Europe in 1998. A reformulated version was approved for European use in 2007.
This postmarketing study, as recommended by the risk management plan, was conducted to confirm the safety of reformulated nonacog alfa in a usual care setting in France. This open-label, noninterventional, prospective, longitudinal postmarketing study comprised 19 French hemophilia centers. Patients with hemophilia B receiving reformulated nonacog alfa for prophylaxis or on-demand treatment were followed up on usual care schedule.
A total of 58 subjects were enrolled, of whom 29 (50%) were less than 18 years of age. Hemophilia was severe (baseline F IX activity < 1%) in 47 (81%) patients. All subjects except one were already treated with reformulated nonacog alfa before enrollment. One subject was receiving reformulated nonacog alfa as immune tolerance induction at time of enrollment. At enrollment, treatment regimen was mainly prophylactic in subjects less than 18 years and on-demand in subjects 18 years or older. Median duration of follow-up in the survey was 3.3 (2.3-3.8) years. The median annualized bleeding rate was 3.9 (1.5-5.2) for prophylaxis regimen and 12.2 (3.9-22.1) for on-demand regimen. One subject, a previously untreated patient, developed F IX inhibitors during follow-up. No allergic reaction, no blood cell agglutination, no lack of efficacy or recovery, and no thrombotic events were reported.
Reformulated nonacog alfa was shown to be safe in a usual care setting.
用于治疗B型血友病的重组凝血因子IX（FIX）诺那凝血素α于1998年在欧洲获批。2007年，一种重新配方的版本获批在欧洲使用。
按照风险管理计划的建议开展了这项上市后研究，以确认重新配方的诺那凝血素α在法国常规护理环境中的安全性。这项开放标签、非干预性、前瞻性、纵向的上市后研究纳入了19个法国血友病治疗中心。接受重新配方的诺那凝血素α进行预防或按需治疗的B型血友病患者按照常规护理计划进行随访。
共纳入58名受试者，其中29名（50%）年龄小于18岁。47名（81%）患者的血友病病情严重（基线FIX活性<1%）。除1名受试者外，所有受试者在入组前已接受重新配方的诺那凝血素α治疗。1名受试者在入组时接受重新配方的诺那凝血素α进行免疫耐受诱导。入组时，年龄小于18岁的受试者治疗方案主要为预防性治疗，18岁及以上受试者为按需治疗。调查中的中位随访时间为3.3（2.3 - 3.8）年。预防性治疗方案的年化出血率中位数为3.9（1.5 - 5.2），按需治疗方案为12.2（3.9 - 22.1）。1名既往未接受治疗的受试者在随访期间出现了FIX抑制物。未报告过敏反应、血细胞凝集、疗效不佳或恢复情况不佳以及血栓形成事件。
在常规护理环境中，重新配方的诺那凝血素α被证明是安全的。
