重度血友病治疗趋势及欧盟血友病监测系统（EUHASS）注册中心对抑制剂评估的影响
Trends in Treatment of Severe Haemophilia and Impact on Inhibitor Assessment by the EUHASS Registry.
作者信息
Fischer Kathelijn, Lassila Riitta, Peyvandi Flora, Gatt Alex, Gouw Samantha C, Hollingsworth Rob, Lambert Thierry, Kaczmarek Radoslaw, Carbonero Diana, Makris Michael
机构信息
Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, University Utrecht, Utrecht, the Netherlands.
Department of Hematology, Unit of Coagulation Disorders, Helsinki University Central Hospital, Research Program Unit in Systems Oncology, University of Helsinki, Helsinki, Finland.
出版信息
Haemophilia. 2025 May;31(3):433-440. doi: 10.1111/hae.70039. Epub 2025 Apr 2.
BACKGROUND
The last 15 years have seen new extended half-life (EHL) recombinant FVIII/IX concentrates and nonreplacement therapy for haemophilia A (emicizumab) introduced in Europe. These changes affect FVIII/IX exposure in previously untreated patients (PUPs) and previously treated patients (PTPs) with severe haemophilia A and B (SHA and SHB) and may modify inhibitor development and/or detection.
AIM
To report trends in treatment for severe haemophilia and concomitant changes in inhibitor incidence.
METHODS
Between 2008 and 2022, 97 centres reported inhibitor development against FVIII/IX concentrates to the European Haemophilia Safety Surveillance System (EUHASS). Inhibitors were reported quarterly, and PUPs without inhibitor development annually. Cumulative inhibitor incidences (95% confidence intervals [CI]) were calculated for PUPs and incidence rates/1000 years (CI) for PTPs.
RESULTS
By 2022, SHA-PUPs (n = 1574) received emicizumab (44%), SHL-rFVIII (21.5%), pdFVIII (17.5%) and EHL-rFVIII (17%). SHB-PUPs (n = 236) received EHL-rFIX (79%) and SHL-rFIX (21%). SHA-PTPs (68,772 years) received EHL-rFVIII (31%), SHL-rFVIII (28%), emicizumab (25%), and pdFVIII (15%). SHB PTPs (11,185 years) received EHL-rFIX (69%), pdFIX (15%) and SHL-rFIX (15%). Observed Inhibitor incidence in SHA-PUPs decreased from 24% before 2016 to 6% in 2022 (p < 0.001), and potentially in SHB-PUPs too (from 9% to 3%; p = 0.066), but remained stable in SHA/SHB PTPs.
CONCLUSION
In 2022, 44% of SHA-PUPs and 25% of SHA-PTPs received emicizumab prophylaxis. Concomitantly, observed inhibitor incidence reduced to 6% in SHA-PUPs. In SHB, EHL-rFIX treatment increased to 79% in SHB-PUPs and 69% in SHB-PTPs. Assessing inhibitor incidence for new concentrates is likely to be hampered by novel treatments causing delayed exposure to FVIII/FIX.
背景
在过去15年里，欧洲引入了新的延长半衰期（EHL）重组FVIII/IX浓缩物以及用于A型血友病的非替代疗法（艾美赛珠单抗）。这些变化影响了先前未治疗的患者（PUPs）以及先前接受过治疗的严重A型和B型血友病患者（SHA和SHB）（即PTPs）的FVIII/IX暴露情况，可能会改变抑制剂的产生和/或检测。
目的
报告严重血友病的治疗趋势以及抑制剂发生率的相应变化。
方法
2008年至2022年期间，97个中心向欧洲血友病安全监测系统（EUHASS）报告了针对FVIII/IX浓缩物的抑制剂产生情况。抑制剂按季度报告，未产生抑制剂的PUPs则每年报告一次。计算了PUPs的累积抑制剂发生率（95%置信区间[CI]）以及PTPs的发生率/每1000年（CI）。
结果
到2022年，SHA-PUPs（n = 1574）接受了艾美赛珠单抗（44%）、高纯度重组FVIII（SHL-rFVIII，21.5%）、血浆源性FVIII（pdFVIII，17.5%）和EHL-rFVIII（17%）。SHB-PUPs（n = 236）接受了EHL-rFIX（79%）和SHL-rFIX（21%）。SHA-PTPs（68772年）接受了EHL-rFVIII（31%）、SHL-rFVIII（28%）、艾美赛珠单抗（25%）和pdFVIII（15%）。SHB-PTPs（11185年）接受了EHL-rFIX（69%）、pdFIX（15%）和SHL-rFIX（15%）。观察到SHA-PUPs中的抑制剂发生率从2016年前的24%降至2022年的6%（p < 0.001），SHB-PUPs可能也出现了下降（从9%降至3%；p = 0.066），但在SHA/SHB-PTPs中保持稳定。
结论
2022年，44%的SHA-PUPs和25%的SHA-PTPs接受了艾美赛珠单抗预防治疗。与此同时，观察到SHA-PUPs中的抑制剂发生率降至6%。在SHB中，EHL-rFIX治疗在SHB-PUPs中增加到79%，在SHB-PTPs中增加到69%。新的浓缩物导致FVIII/FIX暴露延迟，这可能会妨碍对新浓缩物抑制剂发生率的评估。
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