Immune Tolerance Induction (ITI) with a pdFVIII/VWF Concentrate (octanate) in 100 Patients in the Observational ITI (ObsITI) Study

C. Escuriola Ettingshausen, V. Vdovin, N. Zozulya, P. Svirin, T. Andreeva, M. Benedik-Dolničar, V. Jiménez‐Yuste, L. Kitanovski, S. Zupancic-Salek, A. Pavlova, A. Bátorová, Cesar Montaño Mejía, G. Abdilova, S. Knaub, M. Jansen, S. Lowndes, L. Belyanskaya, O. Walter, J. Oldenburg
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引用次数: 1

Abstract

Background  Immune tolerance induction (ITI) with repeated factor VIII (FVIII) administration is the only strategy proven to eradicate inhibitors. The observational ITI study is evaluating ITI with a range of FVIII products. Methods  This subgroup analysis reports prospective interim data for patients treated with a plasma-derived, von Willebrand factor-stabilized FVIII concentrate (pdFVIII/VWF, octanate). Complete success (CS) of ITI required achievement of three criteria: inhibitor titer < 0.6 BU/mL; FVIII recovery ≥ 66%; FVIII half-life ≥6 hours. Partial success (PS) required achievement of two criteria and partial response (PR) one. ITI success was defined as CS or PS. Data were analyzed for patients who achieved CS, had 36 months' observation, or failed ITI. Results  One-hundred prospectively enrolled patients were included in the analysis; 91 had poor prognosis factors for ITI success. The mean (standard deviation) daily ITI dose was 116.4 (61.1) IU FVIII/kg in 14 low responders (< 5 BU/mL) and 173.7 (112.0) IU FVIII/kg in 86 high responders (≥ 5 BU/mL). Inhibitor titers < 0.6 BU/mL were achieved in 71% of patients in a median of 4.01 months, accompanied by a 93% reduction in bleeding rate. ITI success was achieved by 70% of patients and 56 of 72 (78%) primary (first-line) ITI patients. PR was achieved by 5 patients; ITI failed in 25 patients. PS and CS were achieved in a median of 5.55 and 11.25 months, respectively. Conclusions  ITI with pdFVIII/VWF led to rapid eradication of FVIII inhibitors, normalization of FVIII pharmacokinetics in the majority of patients, and a significant reduction in bleeding rates.
在观察性ITI (ObsITI)研究中,100例患者使用pdFVIII/VWF浓缩物(辛酸盐)进行免疫耐受诱导(ITI)
背景免疫耐受诱导(ITI)与重复因子VIII (FVIII)给药是唯一被证明可以根除抑制剂的策略。观察性ITI研究是用一系列FVIII产品评估ITI。该亚组分析报告了使用血浆来源的血管性血友病因子稳定FVIII浓缩物(pdFVIII/VWF,辛酸盐)治疗的患者的前瞻性中期数据。ITI的完全成功(CS)需要满足三个标准:抑制剂滴度< 0.6 BU/mL;FVIII回收率≥66%;FVIII半衰期≥6小时。部分成功(PS)需要达到两个标准和部分反应(PR)一个。ITI成功定义为CS或PS。对达到CS、观察36个月或ITI失败的患者进行数据分析。结果100例前瞻性入组患者纳入分析;91例患者ITI成功预后因素较差。14名低反应者(< 5 BU/mL)的平均每日ITI剂量(标准差)为116.4 (61.1)IU FVIII/kg, 86名高反应者(≥5 BU/mL)的平均每日ITI剂量为173.7 (112.0)IU FVIII/kg。71%的患者在中位4.01个月的时间内达到了抑制剂滴度< 0.6 BU/mL,同时出血率降低了93%。70%的患者ITI成功,72例(78%)原发性(一线)ITI患者中有56例成功。5例患者达到PR;25例患者ITI失败。PS和CS的中位数分别为5.55个月和11.25个月。结论:ITI合并pdFVIII/VWF可快速清除FVIII抑制剂,使大多数患者的FVIII药代动力学正常化,并显著降低出血率。
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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