Holstein K, Batorova A, Carvalho M, Fijnvandraat K, Holme P, Kavakli K, Lambert T, Rocino A, Jiménez-Yuste V, Astermark J
University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
National Hemophilia Center, Dept. of Hematology and Transfusion Medicine, School of Medicine of Comenius University and University Hospital, Bratislava, Slovakia.
Thromb Res. 2016 Dec;148:38-44. doi: 10.1016/j.thromres.2016.10.015. Epub 2016 Oct 15.
Inhibitor development in people with haemophilia is a serious complication that may require intensive and costly interventions. The goal of inhibitor management should be permanent inhibitor eradication through immune tolerance induction (ITI), but well-designed studies are lacking and the management of patients is therefore defined by the experience and views of the clinician.
To explore the current clinical practice and outcome of ITI therapy in Europe and how this may have changed over the last decade, as well as to provide consensus recommendations to guide clinicians in their clinical practice.
A survey was conducted among 16 European haemophilia comprehensive care centres to evaluate current ITI treatment regimens and success rates in severe and mild/moderate haemophilia A and haemophilia B. In addition, an updated literature review was performed as guidance for providing recommendations.
We demonstrated successful inhibitor treatment in 86% of severe haemophilia A patients with low responding (LR) and 59% of patients with high responding (HR) inhibitors. Some new trends in the management of patients with inhibitors were identified, including a tendency to use low-dose regimens (<50IU/kg/d) in both children and adults with HR inhibitors possibly based on similar success rates demonstrated in the I-ITI study compared to a high-dose protocol. Data on ITI therapy in mild and moderate haemophilia as well as haemophilia B were limited.
The outcome of ITI therapy seems to be stable over time, and treatment regimens remain heterogeneous. The use of low dose regimens however is considered more frequently.
血友病患者体内产生抑制剂是一种严重的并发症，可能需要强化且昂贵的干预措施。抑制剂管理的目标应是通过免疫耐受诱导（ITI）实现永久性抑制剂清除，但缺乏精心设计的研究，因此患者的管理取决于临床医生的经验和观点。
探讨欧洲ITI治疗的当前临床实践和结果，以及在过去十年中可能发生的变化，并提供共识性建议以指导临床医生的临床实践。
对16个欧洲血友病综合护理中心进行了一项调查，以评估重度和轻度/中度A型血友病及B型血友病患者当前的ITI治疗方案和成功率。此外，进行了更新的文献综述作为提供建议的指导。
我们证明，86%的低反应（LR）重度A型血友病患者和59%的高反应（HR）抑制剂患者的抑制剂治疗取得了成功。确定了抑制剂患者管理中的一些新趋势，包括在患有HR抑制剂的儿童和成人中倾向于使用低剂量方案（<50IU/kg/d），这可能是基于I-ITI研究中与高剂量方案相比显示出的相似成功率。关于轻度和中度血友病以及B型血友病的ITI治疗数据有限。
随着时间的推移，ITI治疗的结果似乎稳定，治疗方案仍然存在异质性。然而，低剂量方案的使用更为频繁。
