ABT-450, Ritonavir, Ombitasvir, and Dasabuvir Achieves 97% and 100% Sustained Virologic Response With or Without Ribavirin in Treatment-Experienced Patients With HCV Genotype 1b Infection
ABT-450, Ritonavir, Ombitasvir, and Dasabuvir Achieves 97% and 100% Sustained Virologic Response With or Without Ribavirin in Treatment-Experienced Patients With HCV Genotype 1b Infection
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DOI：
10.1053/j.gastro.2014.04.045
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发表时间：
2014-08-01
期刊：
影响因子：
29.4
通讯作者：
Bernstein, Barry
中科院分区：
文献类型：
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作者：
Andreone, Pietro;Colombo, Massimo G.;Bernstein, Barry
背景与目的：ABT-450（一种蛋白酶抑制剂）、利托那韦、奥比他韦（一种NS 5A抑制剂）、达沙布韦（一种非核苷聚合酶抑制剂）和利巴韦林的无干扰素方案已显示出对丙型肝炎病毒（HCV）基因型1b感染（全球最流行的亚型）患者的疗效。我们评估了利巴韦林是否是ABT-450、利托那韦、奥比他韦和达沙布韦在这些患者中产生高持续病毒学应答（SVR）率所必需的。方法：我们进行了一项多中心、开放标签、3期临床试验，纳入了179例既往接受聚乙二醇干扰素和利巴韦林治疗的HCV基因型1b感染、无肝硬化的患者。患者被随机（1：1）分配到ABT-450组，利托那韦，奥比他韦，达沙布韦，与利巴韦林（组1）或没有（组2）12周。主要终点是治疗后12周的SVR（SVR 12）。我们评估了该方案与特拉匹韦、聚乙二醇干扰素和利巴韦林治疗的相似人群的应答率（64%）的非劣效性。研究结果：第1组和第2组的SVR 12发生率均较高，不劣于报告的特拉匹韦、聚乙二醇干扰素和利巴韦林联合治疗的应答率（第1组：96.6%; 95%置信区间，92.8%-100%;第2组：100%; 95%置信区间，95.9%-100%）。第2组的缓解率不劣于第1组。研究期间未发生病毒学失败。2例患者（1.1%）因不良事件终止研究，均在第1组中。第1组和第2组中最常见的不良事件分别为疲乏（31.9% vs 15.8%）和头痛（24.2% vs 23.2%）。血红蛋白水平下降至低于正常下限在第1组中更常见（42.0%对第2组的5.5%; P
BACKGROUND & AIMS: The interferon-free regimen of ABT-450 (a protease inhibitor), ritonavir, ombitasvir (an NS5A inhibitor), dasabuvir (a non-nucleoside polymerase inhibitor), and ribavirin has shown efficacy in patients with hepatitis C virus (HCV) genotype 1b infection-the most prevalent subgenotype worldwide. We evaluated whether ribavirin is necessary for ABT-450, ritonavir, ombitasvir, and dasabuvir to produce high rates of sustained virologic response (SVR) in these patients. METHODS: We performed a multicenter, open-label, phase 3 trial of 179 patients with HCV genotype 1b infection, without cirrhosis, previously treated with peginterferon and ribavirin. Patients were assigned randomly (1:1) to groups given ABT-450, ritonavir, ombitasvir, and dasabuvir, with ribavirin (group 1) or without (group 2) for 12 weeks. The primary end point was SVR 12 weeks after treatment (SVR12). We assessed the noninferiority of this regimen to the rate of response reported (64%) for a similar population treated with telaprevir, peginterferon, and ribavirin. RESULTS: Groups 1 and 2 each had high rates of SVR12, which were noninferior to the reported rate of response to the combination of telaprevir, peginterferon, and ribavirin (group 1: 96.6%; 95% confidence interval, 92.8%-100%; and group 2: 100%; 95% confidence interval, 95.9%-100%). The rate of response in group 2 was noninferior to that of group 1. No virologic failure occurred during the study. Two patients (1.1%) discontinued the study owing to adverse events, both in group 1. The most common adverse events in groups 1 and 2 were fatigue (31.9% vs 15.8%) and headache (24.2% vs 23.2%), respectively. Decreases in hemoglobin level to less than the lower limit of normal were more frequent in group 1 (42.0% vs 5.5% in group 2; P