The B-Natural study-The outcome of immune tolerance induction therapy in patients with severe haemophilia B
The B-Natural study-The outcome of immune tolerance induction therapy in patients with severe haemophilia B
复制标题
DOI：
10.1111/hae.14357
复制
发表时间：
2021-06-12
期刊：
影响因子：
3.9
通讯作者：
Shapiro, Amy D.
中科院分区：
文献类型：
--
作者：
Astermark, Jan;Holstein, Katharina;Shapiro, Amy D.
血友病B（HB）比血友病A（HA）更少发生抑制剂。然而，当存在时，免疫耐受诱导（ITI）治疗的耐受化的成功率较低，并发症的风险higher.Aim评估的使用和结果的ITI在HB和inhibitors.Methods患者包括单例或兄弟姐妹与当前/历史的抑制剂B-自然的观察性研究，旨在增加对HB患者的临床管理的理解。患者随访6个月，人口统计学，医疗和社会史，和治疗的信息recorded.Results 29例严重HB和抑制剂在24个中心。22名患者接受了一个或多个ITI疗程，有或没有免疫抑制。8例患者（36.4%）在ITI的第一个疗程后成功耐受。其中1例成功（12.5%）出现过敏表现，而10例治疗失败的相应数量为5例（50%）。7例大缺失患者中有1例（14.2%）和8例无义突变患者中有3例（37.5%）在首次尝试时耐受，所有发生肾病的患者要么失败要么正在进行中。在研究结束时，11（50%）被认为是成功的耐受后，一个或多个ITI课程，三个不成功，八个仍在接受treatment.Conclusion我们的数据强调的可能性和困难，实现耐受性HB患者与抑制剂。突变类型和并发症似乎与ITI结果相关，但成功ITI的更准确定义是必要的。
Introduction Inhibitors develop less frequently in haemophilia B (HB) than haemophilia A (HA). However, when present, the success of tolerization by immune tolerance induction (ITI) therapy is lower and the risk of complications higher.Aim To evaluate the use and outcome of ITI in patients with HB and inhibitors.Methods Subjects include singletons or siblings with a current/history of inhibitors enrolled in B-Natural-an observational study designed to increase understanding of clinical management of patients with HB. Patients were followed for 6 months and information on demographics, medical and social history, and treatment were recorded.Results Twenty-nine patients with severe HB and inhibitors were enrolled in 24 centres. Twenty-two underwent one or more courses of ITI with or without immune suppression. Eight patients (36.4%) were successfully tolerized after the first course of ITI. One of these successes (12.5%) experienced allergic manifestations, whereas the corresponding number for the 10 treatment failures was five (50%). One of seven (14.2%) patients with large deletions and three of eight (37.5%) with nonsense mutations were tolerized at the first attempt, and all patients experiencing nephrosis either failed or were on-going. At study end, 11 (50%) were considered successfully tolerized after one or more ITI courses, three were unsuccessful, and eight were still undergoing treatment.Conclusion Our data underscore the possibilities and difficulties of achieving tolerization in patients with HB with inhibitors. The type of mutation and complications appear to correlate with ITI outcome, but more accurate definitions of successful ITI are warranted.