High Efficacy of ABT-493 and ABT-530 Treatment in Patients With HCV Genotype 1 or 3 Infection and Compensated Cirrhosis
High Efficacy of ABT-493 and ABT-530 Treatment in Patients With HCV Genotype 1 or 3 Infection and Compensated Cirrhosis
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DOI：
10.1053/j.gastro.2016.07.020
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发表时间：
2016-10-01
期刊：
影响因子：
29.4
通讯作者：
Mensa, Federico J.
中科院分区：
文献类型：
--
作者：
Gane, Edward;Poordad, Fred;Mensa, Federico J.
背景与目的：ABT-493(NS3/4A蛋白水解酶抑制剂)联合ABT-530(NS5A抑制剂)治疗12周后持续病毒学应答率(SVR12)在感染丙型肝炎病毒(GT)1-6的非肝硬变患者中显示出很高的比率。我们描述了两个开放的第二阶段研究，调查ABT-493联合ABT-530联合利巴韦林(RBV)治疗GT1或GT3感染的代偿性肝硬变患者的有效性和安全性。方法：GT1感染患者应用ABT-493 200 mg加ABT-530 120 mg，疗程12周。GT3感染患者随机接受300 mg ABT-493加120 mg ABT-530治疗，每天一次800 mg RBV或不加800 mg RBV治疗12周；有治疗经验的未接受RBV治疗的患者接受16周治疗。疗效用SVR12来衡量，定义为丙型肝炎病毒核糖核酸水平低于25IU/mL。在整个研究过程中对不良事件和实验室参数进行了评估。结果：入选GT1感染患者27例，GT3感染患者55例。大多数人是不接受治疗的(84%)和男性(65%)。在GT1感染的患者中，96%(26/27；95%可信区间82-99)的患者实现了SVR12，1例复发。在感染GT3的患者中，无RBV组(1例复发)的SVR12发生率为96%(27/28，95%CI，82~99)，含RBV组的SVR12发生率为100%(27/27，95%CI，88~100)。最常见的不良反应是头痛、疲劳和恶心。实验室异常很少见；没有患者停止治疗。结论：在合并或不合并RBV的肝硬变患者中，ABT-493联合ABT-530可获得96%-100%的SVR12率，且耐受性良好。
BACKGROUND & AIMS: The combination of ABT-493 (NS3/4A protease inhibitor) plus ABT-530 (NS5A inhibitor) has shown high rates of sustained virologic response at post-treatment week 12 (SVR12) in noncirrhotic patients infected with hepatitis C virus (HCV) genotypes (GTs) 1-6. We describe 2 open-label phase 2 studies investigating the efficacy and safety of ABT-493 plus ABT-530 with or without ribavirin (RBV) in GT1-or GT3-infected patients with compensated cirrhosis. METHODS: Patients with GT1 infection received 200 mg ABT-493 plus 120 mg ABT-530 for 12 weeks. Patients with GT3 infection were randomized 1: 1 to receive 300 mg ABT-493 plus 120 mg ABT-530 with or without once-daily 800 mg RBV for 12 weeks; treatment-experienced patients who were not treated with RBV received 16 weeks of therapy. Efficacy was measured by SVR12, defined as an HCV-RNA level less than 25 IU/mL. Adverse events and laboratory parameters were evaluated throughout the study. RESULTS: Twenty-seven patients with GT1 infection and 55 patients with GT3 infection were enrolled. The majority were treatment-naive (84%) and male (65%). In patients with GT1 infection, SVR12 was achieved by 96% (26 of 27; 95% confidence interval [CI], 82-99) of patients, with 1 relapse. Among GT3-infected patients, SVR12 was achieved in 96% (27 of 28; 95% CI, 82-99) of patients in the RBV-free arm (1 relapse), and in 100% (27 of 27; 95% CI, 88-100) in the RBV-containing arm. The most common adverse events were headache, fatigue, and nausea. Laboratory abnormalities were rare; no patient discontinued treatment. CONCLUSIONS: In cirrhotic HCV GT1-or GT3-infected patients, ABT-493 plus ABT-530 with or without RBV achieved SVR12 rates of 96%-100% and was well tolerated.