Emicizumab prophylaxis: Prospective longitudinal real-world follow-up and monitoring
Emicizumab prophylaxis: Prospective longitudinal real-world follow-up and monitoring
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DOI：
10.1111/hae.14318
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发表时间：
2021-04-23
期刊：
影响因子：
3.9
通讯作者：
Kenet, Gili
中科院分区：
文献类型：
--
作者：
Barg, Assaf A.;Budnik, Ivan;Kenet, Gili
简介：真实世界的数据对预防严重血友病A（HA）患者治疗emicizumab是稀缺的。目的：研究纵向emicizumab预防的有效性和安全性，并评估实验室监测相关性在一个大的patient coherent.Methods：HA患者与FVIII抑制剂，启动emicizumab预防，前瞻性招募。记录出血、不良事件和手术。结果：共有107例患者，其中包括58名儿童（其中位数（IQR）年龄为6（1-11）岁）与严重HA，组成了研究队列。29%（31/107）的HA患者存在FVIII抑制物。患者的中位随访时间为67周（最长144周）。53例患者的中位随访时间为53周，无出血。儿童中的大多数出血（94%）与创伤有关，而61%的成人持续自发性关节出血。4例患者发生了大出血，1例婴儿出现了致死性结局，该婴儿还出现了中心静脉管路血栓形成。未发生其他严重不良事件。7名患者因各种原因决定停止emicizumab治疗。在emicizumab预防性治疗开始后，emicizumab血浆水平升高，除1例疑似抗药抗体的患者外，所有患者的血浆水平在随访期间保持不变。在抑制物患者中观察到FVIII抑制物水平显著降低。TG增加和持续，但不能presticate出血risk.Conclusion：Emicizumab预防大多耐受良好，虽然50%的患者经历了突破性出血。常规TG监测不是强制性的，需要在选定的患者人群中进行进一步研究。
Introduction: Real-world data on prophylaxis of severe haemophilia A (HA) patients treated by emicizumab are scarce.Aim: To study the efficacy and safety of longitudinal emicizumab prophylaxis and assess laboratory monitoring correlations in a large patient cohort.Methods: HA patients with and without FVIII inhibitors, initiating emicizumab prophylaxis, were prospectively enrolled. Bleeding, adverse events and surgeries were documented. FVIII inhibitors, emicizumab levels and thrombin generation ( TG) were sequentially measured.Results: A total of 107 patients, including 58 children (whose median (IQR) age was 6 (1-11) years) with severe HA, composed the study cohort. Twenty-nine per cent (31/107) of our HA patients had FVIII inhibitors. Patients were followed for a median of 67 weeks (up to 144 weeks). Fifty-three patients, whose median follow-up was 53 weeks, experienced zero bleeds. Most bleeds (94%) among children were trauma-related, whereas 61% of adults sustained spontaneous joint bleeds. Four patients experienced major bleeds, with a fatal outcome in one infant, who also presented with central venous line thrombosis. No other serious adverse events were encountered. Seven patients have decided to stop emicizumab treatment for various reasons. Emicizumab plasma levels increased after emicizumab prophylaxis initiation, and values were maintained during follow-up, in all but one patient, suspected of anti-drug antibodies. A significant reduction of FVIII inhibitor levels was noted among inhibitor patients. TG was increased and sustained yet could not prognosticate bleeding risk.Conclusion: Emicizumab prophylaxis was mostly well tolerated, although 50% of patients experienced breakthrough bleeds. Routine TG monitoring is not obligatory, and further studies are warranted in selected patient populations.