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首页> 外文期刊>Thrombosis and Haemostasis: Journal of the International Society on Thrombosis and Haemostasis >Increased inhibitor incidence in severe haemophilia A since 1990 attributable to more low titre inhibitors
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Increased inhibitor incidence in severe haemophilia A since 1990 attributable to more low titre inhibitors

机译：自1990年以来，重度滴度抑制剂的降低导致严重A型血友病抑制剂的发生率增加

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Many studies have reported an increased incidence of inhibitors in previously untreated patients (PUPs) with severe haemophilia A after the introduction of recombinant products. It was the objective of this study to investigate whether the inhibitor incidence has increased between 1990 and 2009 in an unselected cohort of PUPs with severe haemophilia A (FVIII< 1 %). Patients were consecutively recruited from 31 haemophilia treatment centres in 16 countries and followed until 50 exposure days or until inhibitor development. Inhibitor development was studied in five-year birth cohorts comparing cumulative incidences. Furthermore the risk for inhibitor development per five-year birth cohort was studied using multivariable Cox regression, adjusting for potential genetic and treatment-related confounders. A total of 926 PUPs were included with a total cumulative inhibitor incidence of 27.5 %. The inhibitor incidence increased from 19.5 % in 1990-1994 (lowest) to 30.9 % in 2000-2004 (highest; p-value 0.011). Low titre inhibitor incidence increased from 3.1 % in 1990-1994 to 10.5 % in 2005-2009 (p-value 0.009). High titre inhibitor incidences remained stable over time. After 2000, risk of all inhibitor development was increased with adjusted hazard ratios 1.96 (95 % CI 1.06-2.83) in 2000-2004 and 2.34 (1.42-4.92) in 2005-2009. Screening for inhibitors was intensified over this 20-year study period from a median of 1.9 to 2.9 tests/year before 2000 to 2.7 to 4.3 tests/year after 2000. In conclusion, the cumulative inhibitor incidence has significantly increased between 1990 and 2009. The high titre inhibitor incidence has remained stable.
机译：许多研究报告说，在引入重组产品后，先前未经治疗的严重A型血友病患者（PUP）中抑制剂的发生率增加。这项研究的目的是调查在1990年至2009年之间未选择的一组严重A型血友病（FVIII <1％）的PUPs中抑制剂的发生率是否增加。从16个国家/地区的31个血友病治疗中心连续招募患者，并随访至暴露50天或抑制剂形成为止。在五年出生队列中研究了抑制剂的发展，比较了累积发生率。此外，使用多变量Cox回归研究了每五年出生队列抑制剂发展的风险，并针对潜在的遗传和与治疗相关的混杂因素进行了调整。总共包括926个PUP，累计抑制剂发生率为27.5％。抑制剂的发生率从1990-1994年的19.5％（最低）增加到2000-2004年的30.9％（最高; p值0.011）。低滴度抑制剂的发生率从1990-1994年的3.1％增加到2005-2009年的10.5％（p值0.009）。高滴度抑制剂的发生率随时间保持稳定。 2000年之后，所有抑制剂形成的风险均随着2000-2004年的危险比1.96（95％CI 1.06-2.83）和2005-2009年的2.34（1.42-4.92）调整而增加。在这20年的研究期间，对抑制剂的筛选从2000年之前的每年1.9到2.9测试/年增加到2000年之后的2.7到4.3测试/年。总体而言，在1990年到2009年之间，抑制剂的累积发病率显着增加。高滴度抑制剂的发病率一直保持稳定。

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