Hemophilia Care Centre, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Hemophilia Care Centre, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Haemophilia. 2022 Jan;28(1):65-72. doi: 10.1111/hae.14456. Epub 2021 Nov 19.
Immune Tolerance Induction (ITI) is the first-choice therapy to eradicate Factor VIII (FVIII) neutralizing antibodies in patients with haemophilia A (HA). There is limited published data on ITI from East Mediterranean countries.
To assess the effectiveness of a low-dose ITI regimen to eradicate FVIII neutralizing antibodies in children with severe HA and high-titre inhibitors.
A prospective, single-arm study was conducted in children with HA (FVIII < 1 IU/dl), high-titre inhibitors and poor prognostic factors for successful ITI. Patients were treated with ∼50 IU/kg plasma-derived FVIII containing von Willebrand factor (pdFVIII/VWF) concentrate (Koate-DVI, Grifols) three times a week. Time to achieve tolerance, total and partial success were analysed after ITI. Annual bleeding rate (ABR), number of target joints, FVIII recovery and school absence were compared before and after ITI.
Twenty patients with median (range) age of 6.2 (3-12) years and pre-ITI inhibitor titre of 36.5 (12-169) BU were enrolled. ITI lasted ≤12 months (early tolerization) in 45% of patients. Median follow-up was 12 months (3-22) and total response rate was 80% (60% total success; 20% partial success). Patients with two and three poor prognosis factors achieved overall success rate of 60% and 50%, respectively. ABR, target joints and school absence were reduced after ITI by 60%, 50% and 44.1%, respectively. In successful ITI tolerized patients, FVIII recovery was 90 (60-100)%.
A low-dose ITI therapy using a pdFVIII/VWF concentrate achieved at least partial tolerance in 80% of patients, and reduced annual bleeds in children with high inhibitor titres and at least one poor prognosis factor for ITI treatment success.
免疫耐受诱导（ITI）是血友病 A（HA）患者消除因子 VIII（FVIII）中和抗体的首选疗法。来自东地中海国家的关于 ITI 的已发表数据有限。
评估低剂量 ITI 方案在伴有严重 HA 和高滴度抑制剂的儿童中消除 FVIII 中和抗体的有效性。
对具有 HA（FVIII <1 IU/dl）、高滴度抑制剂和 ITI 治疗成功的不良预后因素的儿童进行前瞻性、单臂研究。患者每周接受 3 次含血管性血友病因子（von Willebrand factor，VWF）的血浆源性 FVIII（pdFVIII/VWF）浓缩物（Grifols 公司的 Koate-DVI），剂量约为 50 IU/kg。在 ITI 后分析达到耐受的时间、总成功率和部分成功率。比较 ITI 前后每年出血率（ABR）、目标关节数、FVIII 恢复情况和缺课情况。
共纳入 20 例年龄中位数（范围）为 6.2（3-12）岁、ITI 前抑制剂滴度为 36.5（12-169）BU 的患儿。45%的患者 ITI 持续时间≤12 个月（早期耐受）。中位随访时间为 12 个月（3-22），总反应率为 80%（60%总成功率；20%部分成功率）。具有两个和三个不良预后因素的患者总成功率分别为 60%和 50%。ITI 后 ABR、目标关节和缺课分别减少了 60%、50%和 44.1%。在成功耐受 ITI 的患者中，FVIII 恢复率为 90（60-100）%。
使用 pdFVIII/VWF 浓缩物的低剂量 ITI 治疗方案在 80%的患者中至少达到部分耐受，并减少了具有高抑制剂滴度和至少一个 ITI 治疗成功不良预后因素的儿童的年出血次数。
