Oldenburg J, Austin S K, Kessler C M
Institute for Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.
Haemophilia. 2014 Sep;20 Suppl 6:17-26. doi: 10.1111/hae.12466.
The development of alloantibody inhibitors against factor VIII (FVIII) represents the most significant complication of haemophilia care. Inhibitors tend to develop early in the course of treatment in about 20-30% of patients with severe haemophilia who receive on-demand or prophylactic FVIII therapy. Many factors are associated with inhibitor formation, including disease severity, major FVIII gene defects, family history and non-Caucasian race, as well as age at first treatment, intensity of early treatment, use of prophylaxis and product choice. As these latter treatment-related variables are modifiable, they provide opportunity to minimize inhibitor incidence at the clinical level. Data from the Bonn Centre in Germany have indicated an overall success rate of 78% for immune tolerance induction (ITI) therapy, with a failure rate of 15% and with some treatments either ongoing (3%) or withdrawn (4%). Similarly, data from the G-ITI study, the largest international multicentre ITI study using a single plasma-derived (pd) FVIII/von Willebrand factor (VWF) product, have demonstrated success rates (complete and partial) in primary and rescue ITI of 87% and 74%, respectively, with 85% of poor prognosis patients achieving success. Favourable clinical results based on success rates and time to tolerization continue to be reported for use of pdFVIII/VWF in ITI, with pdFVIII/VWF having a particular role in patients who require rescue ITI and those with a poor prognosis for success. Data from prospective, randomized, controlled clinical studies, such as RES.I.ST (Rescue Immune Tolerance Study), are eagerly awaited. Another factor to consider with ITI therapy is cost; preliminary data from an updated decision analytic model have provided early evidence that ITI has an economic advantage compared with on-demand or prophylactic therapy.
针对凝血因子VIII（FVIII）的同种异体抗体抑制剂的出现是血友病治疗中最严重的并发症。在接受按需或预防性FVIII治疗的重度血友病患者中，约20%-30%的患者在治疗过程早期容易产生抑制剂。许多因素与抑制剂的形成有关，包括疾病严重程度、主要FVIII基因缺陷、家族史、非白种人种族，以及首次治疗时的年龄、早期治疗强度、预防措施的使用和产品选择。由于这些与治疗相关的变量是可以改变的，因此它们为在临床层面将抑制剂发生率降至最低提供了机会。德国波恩中心的数据表明，免疫耐受诱导（ITI）疗法的总体成功率为78%，失败率为15%，还有一些治疗正在进行（3%）或已中止（4%）。同样，G-ITI研究（使用单一血浆源性（pd）FVIII/血管性血友病因子（VWF）产品的最大规模国际多中心ITI研究）的数据显示，原发性和挽救性ITI的成功率（完全和部分）分别为87%和74%，85%预后不良的患者获得成功。基于成功率和达到耐受所需时间的良好临床结果继续被报道用于ITI中pdFVIII/VWF的使用，pdFVIII/VWF在需要挽救性ITI的患者和预后不良的患者中具有特殊作用。来自前瞻性、随机、对照临床研究（如RES.I.ST（挽救免疫耐受研究））的数据备受期待。ITI疗法另一个需要考虑的因素是成本；更新后的决策分析模型的初步数据提供了早期证据，表明与按需或预防性治疗相比，ITI具有经济优势。
