背景:Emicizumab被用作皮下预防,用于预防有或没有抑制剂的A型血友病(HA)患者的出血事件。虽然在临床试验中观察到低出血率,在现实世界中,患者使用埃米珠单抗仍然会出现突破性出血(BTB).目前的指南建议使用重组激活因子VII(rFVIIa)治疗抑制剂患者的BTB。由于在HAVEN1研究中观察到的血栓事件,应谨慎使用活化的凝血酶原复合物浓缩物(aPCC)。
目的:本综述的目的是确定和讨论BTB的频率和同时使用rFVIIa的安全性的真实世界数据。
方法:2022年7月15日对以下数据库进行了搜索:BIOSISPreviews®,CurrentContentsSearch®,Embase®,MEDLINE®。搜索词包括\'真实世界\',\'A型血友病\',和\'emicizumab\'。
结论:确定了11篇相关出版物(7篇原创研究文章和4篇大会摘要)。三篇出版物中描述了特异性针对具有抑制剂的HA患者的BTB的频率,其中5%-56%的emicizumab患者报告≥1次出血发作。这些BTB的治疗似乎是根据相关指南进行管理的。重要的是,同时使用rFVIIa期间未发生血栓性并发症.由于现实世界研究的性质,研究之间结果的直接比较是有限的。然而,真实世界的数据显示,在emicizumab预防期间,抑制剂患者中的BTB可以安全地使用rFVIIa治疗.
BACKGROUND: Emicizumab is used as a subcutaneous prophylaxis for prevention of bleeding episodes in patients with haemophilia A (HA) with and without inhibitors. While low bleeding rates were observed in clinical trials, patients still experience breakthrough bleeds (BTBs) with emicizumab in the real-world. Current guidelines recommend use of recombinant activated factor VII (rFVIIa) for treatment of BTBs in patients with inhibitors. Due to thrombotic events observed in the HAVEN 1 study, activated prothrombin complex concentrate (aPCC) should be used with caution.
OBJECTIVE: The objective of this review is to identify and discuss real-world data on the frequency of BTBs and the safety of concomitant rFVIIa use in patients with inhibitors on emicizumab prophylaxis.
METHODS: A search of the following databases was conducted on 15 July 2022: BIOSIS Previews® , Current Contents Search® , Embase® , MEDLINE® . Search terms included \'real world\', \'haemophilia A\', and \'emicizumab\'.
CONCLUSIONS: Eleven relevant publications were identified (seven original research articles and four congress abstracts). The frequency of BTBs specifically for HA patients with inhibitors was described in three publications with 5%-56% patients on emicizumab reporting ≥1 bleeding episode. Treatment of these BTBs appeared to be managed according to relevant guidelines. Importantly, no thrombotic complications occurred during concomitant rFVIIa use. Due to the nature of real-world studies, direct comparison of the results between studies is limited. However, real-world data show that BTBs in inhibitor patients during emicizumab prophylaxis can be safely treated with rFVIIa.