Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
J Thromb Haemost. 2022 Nov;20(11):2526-2537. doi: 10.1111/jth.15878. Epub 2022 Sep 26.
Immune tolerance induction (ITI) is the treatment of choice for eradication of anti-factor VIII (FVIII) neutralizing alloantibodies (inhibitors) in people with inherited hemophilia A and high-responding inhibitor (PwHA-HRi). The association between ITI outcome and time elapsed between inhibitor detection and start of ITI (∆t ) is debatable.
The aim of this study was to evaluate this association among a large cohort of severe PwHA-HRi.
Severe (factor VIII activity level <1%) PwHA-HRi on ITI (n = 142) were enrolled in 15 hemophilia treatment centers. PwHA-HRi were treated according to the Brazilian ITI Protocol. ITI outcomes were defined as success (i.e., recovered responsiveness to exogenous FVIII) and failure (i.e., no responsiveness to exogenous FVIII and requirement of bypassing agents to control bleeding).
Median ages at inhibitor detection and at ITI start were 3.2 years (interquartile range [IQR], 1.6-8.1) and 6.9 years [IQR, 2.6-20.1), respectively. PwHA-HRi were stratified according to ∆t quartiles: first (0.0-0.6 year), second (>0.6-1.7 year), third (>1.7-9.2 years), and fourth quartile (>9.2-24.5 years). The overall success rate was 65.5% (93/142), with no difference among first, second, third, and fourth quartiles (62.9%, 69.4%, 58.3%, and 71.4%, respectively) even after adjusting the analyses for potential confounders.
In conclusion, delayed ITI start is not associated with failure of ITI in PwHA-HRi. Therefore, ITI should be offered for these patients, regardless of the time elapsed between the detection of inhibitor and the ITI start.
免疫耐受诱导（ITI）是治疗遗传性血友病 A 患者和高反应性抑制剂（PwHA-HRi）消除抗因子 VIII（FVIII）中和性自身抗体（抑制剂）的首选方法。抑制剂检测到 ITI 开始之间的时间（∆t）与 ITI 结果之间的关系存在争议。
本研究旨在评估大量严重 PwHA-HRi 患者中的这种关联。
在 15 个血友病治疗中心招募了正在接受 ITI 的严重（FVIII 活性水平<1%）PwHA-HRi（n=142）。PwHA-HRi 根据巴西 ITI 方案进行治疗。ITI 结果定义为成功（即对外源性 FVIII 恢复反应性）和失败（即对外源性 FVIII 无反应性和需要旁路药物来控制出血）。
抑制剂检测和 ITI 开始时的中位年龄分别为 3.2 岁（四分位距 [IQR]，1.6-8.1）和 6.9 岁[IQR，2.6-20.1]。PwHA-HRi 根据 ∆t 四分位数分层：第一四分位数（0.0-0.6 年）、第二四分位数（>0.6-1.7 年）、第三四分位数（>1.7-9.2 年）和第四四分位数（>9.2-24.5 年）。总体成功率为 65.5%（93/142），第一、二、三、四分位数之间无差异（分别为 62.9%、69.4%、58.3%和 71.4%），即使在调整潜在混杂因素后进行分析也是如此。
总之，延迟 ITI 开始与 PwHA-HRi 中 ITI 的失败无关。因此，无论抑制剂检测到 ITI 开始之间的时间如何，都应向这些患者提供 ITI。
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