Trends in Treatment of Severe Haemophilia and Impact on Inhibitor Assessment by the EUHASS Registry.

IF 3 2区医学 Q2 HEMATOLOGY

Haemophilia Pub Date : 2025-04-02 DOI:10.1111/hae.70039

Kathelijn Fischer, Riitta Lassila, Flora Peyvandi, Alex Gatt, Samantha C Gouw, Rob Hollingsworth, Thierry Lambert, Radoslaw Kaczmarek, Diana Carbonero, Michael Makris

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引用次数: 0

Abstract

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.

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重度血友病的治疗趋势及其对EUHASS抑制剂评估的影响。

背景：在过去的15年中，欧洲引入了新的延长半衰期（EHL）重组FVIII/IX浓缩物和非替代治疗血友病A（半珠单抗）。这些变化影响严重血友病A和B （SHA和SHB）以前未治疗的患者（PUPs）和以前治疗过的患者（PTPs）的FVIII/IX暴露，并可能改变抑制剂的发展和/或检测。目的：报道严重血友病的治疗趋势和伴随抑制剂发病率的变化。方法：在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浓缩物的抑制剂开发。抑制剂每季度报告一次，未开发抑制剂的pup每年报告一次。计算PUPs的累积抑制剂发病率（95%置信区间[CI]）和PTPs的发病率/1000年（CI）。结果：到2022年，SHA-PUPs （n = 1574）接受了emicizumab（44%）、SHL-rFVIII（21.5%）、pdFVIII（17.5%）和EHL-rFVIII（17%）。236只shb - pup分别接受EHL-rFIX治疗（79%）和SHL-rFIX治疗（21%）。sha - ptp患者（68,772岁）接受EHL-rFVIII（31%）、SHL-rFVIII（28%）、emicizumab（25%）和pdFVIII（15%）治疗。SHB PTPs（11,185年）接受EHL-rFIX（69%）、pdFIX（15%）和SHL-rFIX（15%）治疗。观察到的抑制剂在SHA-PUPs中的发病率从2016年之前的24%下降到2022年的6% (p < 0.001)，并且在SHB-PUPs中也可能下降(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 - pup和25%的SHA-PTPs接受了emicizumab预防。同时，在sha - pup中观察到抑制剂的发生率降至6%。在SHB中，EHL-rFIX治疗在SHB- pup中增加到79%，在SHB- ptps中增加到69%。评估新浓缩物抑制剂的发生率可能会受到新治疗方法的阻碍，这些新治疗方法会导致FVIII/FIX的延迟暴露。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Haemophilia 医学-血液学

CiteScore

6.50

自引率

28.20%

发文量

226

审稿时长

3-6 weeks

期刊介绍： Haemophilia is an international journal dedicated to the exchange of information regarding the comprehensive care of haemophilia. The Journal contains review articles, original scientific papers and case reports related to haemophilia care, with frequent supplements. Subjects covered include: clotting factor deficiencies, both inherited and acquired: haemophilia A, B, von Willebrand''s disease, deficiencies of factor V, VII, X and XI replacement therapy for clotting factor deficiencies component therapy in the developing world transfusion transmitted disease haemophilia care and paediatrics, orthopaedics, gynaecology and obstetrics nursing laboratory diagnosis carrier detection psycho-social concerns economic issues audit inherited platelet disorders.