非严重血友病抑制剂的发展：来自欧洲血友病安全监测（EUHASS）登记的数据

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis Pub Date : 2025-05-01 DOI:10.1016/j.rpth.2025.102887

Kathelijn Fischer , Riitta Lassila , Flora Peyvandi , Alexander Gatt , Samantha C. Gouw , Robert Hollingsworth , Thierry Lambert , Radek Kaczmarek , Diana Carbonero Alvarez , Michael Makris , EUHASS participants

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引用次数: 0

摘要

背景：关于非严重血友病中抑制剂的发展及其与凝血因子浓缩类型的关系的信息有限。目的在欧洲血友病安全监测系统中评估非严重血友病A （HA）和血友病B （HB）患者抑制剂的发展情况。方法每年报告抑制剂和总治疗病例。每年任何接触浓缩物的时间都被认为是一个治疗年。根据浓缩物类型计算每1000治疗年的发病率和95% ci，并使用发病率比（IRRs）进行比较。结果在2008年至2023年期间，90个中心报告了36074 （HA）和9238 （HB）治疗年。非严重血凝素接收因子(F)VIII的抑制剂率为4.2 / 1000治疗年（95% CI, 3.5-4.9）。中位暴露40天后，中位47.5年（P25-P75 [IQR], 17.0-69.0）出现抑制剂。IQR, 17-80)，其中58%发生50例ed， 88%发生100例ed。总体而言，抑制剂组149例患者中有4例（2.7%）为女性。在一名女性患者中，仅报道了一种非严重HB抑制剂（FIX 7%， 6次ed后），导致每1000治疗年的抑制剂率为0.1 （95% CI, 0.0-0.6）。与标准半衰期重组FVIII相比，血浆源性FVIII的抑制率(IRR, 0.27；95% ci, 0.11-0.58；P & lt;.001)和延长的半衰期FVIII (IRR, 0.18；95% ci, 0.02-0.68；P = .002)显著降低。结论：在非严重血友病中，HA患者每1000治疗年使用抑制剂4.2例，HB患者每1000治疗年使用抑制剂0.1例。与标准半衰期FVIII相比，血浆源性和延长半衰期FVIII的抑制剂显影减少。这些数据表明，抑制剂监测与男女非严重HA相关，应终生持续。

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Inhibitor development in nonsevere hemophilia: data from the European Haemophilia Safety Surveillance (EUHASS) registry

Background

Information on inhibitor development in nonsevere hemophilia and its association with clotting factor concentrate type is limited.

Objectives

To assess inhibitor development in patients with nonsevere hemophilia A (HA) and hemophilia B (HB) in the European Haemophilia Safety Surveillance system.

Methods

Inhibitors and total treated patients are reported annually. Any exposure to concentrate per year was considered a treatment year. Incidence rates per 1000 treatment years and 95% CIs were calculated according to type of concentrate and compared using incidence rate ratios (IRRs).

Results

During 2008 to 2023, 90 centers reported on 36,074 (HA) and 9238 (HB) treatment years. The inhibitor rate for nonsevere HA receiving factor (F)VIII was 4.2 per 1000 treatment years (95% CI, 3.5-4.9). Inhibitors developed at median 47.5 years (P25-P75 [IQR], 17.0-69.0), after median 40 exposure days (EDs; IQR, 17-80), with 58% occurring <50 EDs and 88% <100 EDs. Overall, 4 of 149 (2.7%) patients in the inhibitor group were female. Only one inhibitor was reported in nonsevere HB, in a female patient (FIX 7%, after 6 EDs), resulting in an inhibitor rate of 0.1 per 1000 treatment years (95% CI, 0.0-0.6). Compared with standard half-life recombinant FVIII, inhibitor rates on both plasma-derived FVIII (IRR, 0.27; 95% CI, 0.11-0.58; P < .001) and extended half-life FVIII (IRR, 0.18; 95% CI, 0.02-0.68; P = .002) were significantly reduced.

Conclusion

Inhibitors in nonsevere hemophilia occurred at a rate of 4.2 per 1000 treatment years in HA and 0.1 per 1000 treatment years in HB. Compared with standard half-life FVIII, inhibitor development on plasma-derived and extended half-life FVIII were reduced. These data show that inhibitor monitoring is relevant with nonsevere HA in both sexes and should be continued lifelong.

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