接受艾美赛珠单抗治疗的A型血友病患者中的凝血因子VIII抑制剂：结局的纵向随访
Factor VIII inhibitors in hemophilia A treated with emicizumab: longitudinal follow-up of outcomes.
作者信息
Levy-Mendelovich Sarina, Atia Nitzan, Budnik Ivan, Barg Assaf Arie, Avishai Einat, Cohen Omri, Brutman-Barazani Tami, Livnat Tami, Kenet Gili
机构信息
National Hemophilia Center and Coagulation Unit, Sheba Medical Center, Tel Hashomer, Israel.
Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
出版信息
Res Pract Thromb Haemost. 2023 Jun 14;7(4):100278. doi: 10.1016/j.rpth.2023.100278. eCollection 2023 May.
BACKGROUND
Using emicizumab in lieu of immune tolerance induction (ITI) for patients with hemophilia A (HA) and factor (F)VIII inhibitors has been well described. However, decisions regarding ITI initiation, regimen, and preservation of tolerance remain to be elucidated.
OBJECTIVES
To study the course of FVIII inhibitors in patients with HA and a history of FVIII inhibitors receiving emicizumab prophylaxis.
METHODS
Patients with HA, with and without FVIII inhibitors, initiating emicizumab prophylaxis were prospectively followed up in our center. All patients with current or previous inhibitors were included in this analysis. Plasma samples for FVIII inhibitor assays were obtained every 3 to 6 months or following FVIII exposure. Patients documented annual bleeding rate and any FVIII exposure days (EDs).
RESULTS
Of 162 emicizumab-treated participants, 51 met the inclusion criteria. A decrease in annual bleeding rate was observed in all 51 participants followed up for a median of 3.3 years, with 31 breakthrough bleeding episodes reported in 22 of 51 participants. FVIII inhibitor level transiently increased following FVIII exposures in 5 of 15 failed ITI participants. Eight of 21 participants who did not undergo ITI were exposed to FVIII (1-2 EDs)), and 1 of these 8 participants demonstrated increased FVIII inhibitor levels after head trauma (following 1 ED). Among participants who underwent successful ITI, 8 of 15 patients were exposed to FVIII over a total of 13 EDs (1-2 ED(s) each) for traumatic breakthrough bleeds. In all these participants, inhibitor levels remained zero, indicating successful tolerance maintenance.
CONCLUSION
Our longitudinal follow-up of emicizumab-treated patients with HA and FVIII inhibitors shows that occasional exposure to FVIII may induce a transient anamnestic response. Nonetheless, no FVIII inhibitor recurrence was noted following FVIII exposures in patients who underwent successful ITI.
背景
使用艾美赛珠单抗替代免疫耐受诱导（ITI）用于治疗甲型血友病（HA）和伴有因子（F）VIII抑制物的患者，这一情况已有充分描述。然而，关于ITI启动、方案以及耐受性维持的决策仍有待阐明。
目的
研究接受艾美赛珠单抗预防治疗且有FVIII抑制物病史的HA患者中FVIII抑制物的变化过程。
方法
在我们中心对开始接受艾美赛珠单抗预防治疗的HA患者（有或无FVIII抑制物）进行前瞻性随访。所有目前或既往有抑制物的患者均纳入本分析。每3至6个月或在FVIII暴露后采集血浆样本进行FVIII抑制物检测。患者记录年度出血率和任何FVIII暴露天数（EDs）。
结果
在162例接受艾美赛珠单抗治疗的参与者中，51例符合纳入标准。在随访时间中位数为3.3年的所有51例参与者中，均观察到年度出血率下降，51例参与者中有22例报告了31次突破性出血事件。15例ITI失败的参与者中有5例在FVIII暴露后FVIII抑制物水平短暂升高。21例未接受ITI的参与者中有8例暴露于FVIII（1 - 2个EDs），这8例参与者中有1例在头部外伤后（1个ED后）FVIII抑制物水平升高。在成功进行ITI的参与者中，15例患者中有8例因创伤性突破性出血共暴露于FVIII 13个EDs（每次1 - 2个ED）。在所有这些参与者中，抑制物水平保持为零，表明耐受性维持成功。
结论
我们对接受艾美赛珠单抗治疗的HA和FVIII抑制物患者的纵向随访表明，偶尔暴露于FVIII可能会诱导短暂的回忆反应。尽管如此，成功进行ITI的患者在FVIII暴露后未观察到FVIII抑制物复发。
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