Fischer Kathelijn, Lassila Riitta, Peyvandi Flora, Gatt Alexander, Gouw Samantha C, Hollingsworth Robert, Lambert Thierry, Kaczmarek Radek, Alvarez Diana Carbonero, Makris Michael
Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, University Utrecht, the Netherlands.
PedNet Haemophilia Research Foundation, Baarn, the Netherlands.
Res Pract Thromb Haemost. 2025 May 17;9(4):102887. doi: 10.1016/j.rpth.2025.102887. eCollection 2025 May.
Information on inhibitor development in nonsevere hemophilia and its association with clotting factor concentrate type is limited.
To assess inhibitor development in patients with nonsevere hemophilia A (HA) and hemophilia B (HB) in the European Haemophilia Safety Surveillance system.
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).
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; < .001) and extended half-life FVIII (IRR, 0.18; 95% CI, 0.02-0.68; = .002) were significantly reduced.
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.
关于非重度血友病患者中抑制物产生情况及其与凝血因子浓缩物类型之间关联的信息有限。
在欧洲血友病安全监测系统中评估非重度甲型血友病（HA）和乙型血友病（HB）患者中抑制物的产生情况。
每年报告抑制物情况和接受治疗的患者总数。每年任何一次浓缩物暴露均视为一个治疗年。根据浓缩物类型计算每1000个治疗年的发病率及95%置信区间，并使用发病率比（IRR）进行比较。
在2008年至2023年期间，90个中心报告了36074个（HA）和9238个（HB）治疗年。接受凝血因子（F）VIII治疗的非重度HA患者中，抑制物发生率为每1000个治疗年4.2例（95%置信区间，3.5 - 4.9）。抑制物产生的中位年龄为47.5岁（第25百分位数 - 第75百分位数[四分位间距]，17.0 - 69.0），中位暴露天数（EDs）为40天（四分位间距，17 - 80），其中58%发生在<50个EDs时，88%发生在<100个EDs时。总体而言，抑制物组的149例患者中有4例（2.7%）为女性。非重度HB仅报告了1例抑制物产生，为1名女性患者（FIX 7%，6个EDs后），导致抑制物发生率为每1000个治疗年0.1例（95%置信区间，0.0 - 0.6）。与标准半衰期重组FVIII相比，血浆源性FVIII（IRR，0.27；95%置信区间，0.11 - 0.58；P <.001）和延长半衰期FVIII（IRR，0.18；95%置信区间，0.02 - 0.68；P =.002）的抑制物发生率均显著降低。
非重度血友病中，HA的抑制物发生率为每1000个治疗年4.2例，HB为每1000个治疗年0.1例。与标准半衰期FVIII相比，血浆源性和延长半衰期FVIII的抑制物产生情况减少。这些数据表明，抑制物监测对非重度HA的男性和女性患者均有意义，且应终身持续进行。
