Ann Intern Med. 2015 Jul 7;163(1):1-13. doi: 10.7326/M15-0785.
Novel interferon- and ribavirin-free regimens are needed to treat hepatitis C virus (HCV) infection.
To evaluate the safety and efficacy of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor) in treatment-naive patients.
Randomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02105467).
60 centers in the United States, Europe, Australia, Scandinavia, and Asia.
Cirrhotic and noncirrhotic treatment-naive adults with genotype 1, 4, or 6 infection.
Oral, once-daily, fixed-dose grazoprevir 100 mg/elbasvir 50 mg for 12 weeks, stratified by fibrosis and genotype. Patients were randomly assigned 3:1 to immediate or deferred therapy.
Proportion of patients in the immediate-treatment group achieving unquantifiable HCV RNA 12 weeks after treatment (SVR12); adverse events in both groups.
Among 421 participants, 194 (46%) were women, 157 (37%) were nonwhite, 382 (91%) had genotype 1 infection, and 92 (22%) had cirrhosis. Of 316 patients receiving immediate treatment, 299 of 316 (95% [95% CI, 92% to 97%]) achieved SVR12, including 144 of 157 (92% [CI, 86% to 96%]) with genotype 1a, 129 of 131 (99% [CI, 95% to 100%]) with genotype 1b, 18 of 18 (100% [CI, 82% to 100%]) with genotype 4, 8 of 10 (80% [CI, 44% to 98%]) with genotype 6, 68 of 70 (97% [CI, 90% to 100%]) with cirrhosis, and 231 of 246 (94% [CI, 90% to 97%]) without cirrhosis. Virologic failure occurred in 13 patients (4%), including 1 case of breakthrough infection and 12 relapses, and was associated with baseline NS5A polymorphisms and emergent NS3 or NS5A variants or both. Serious adverse events occurred in 9 (2.8%) and 3 (2.9%) patients in the active and placebo groups, respectively (difference <0.05 percentage point [CI, -5.4 to 3.1 percentage points]); none were considered drug related. The most common adverse events in the active group were headache (17%), fatigue (16%), and nausea (9%).
The study lacked an active-comparator control group and included relatively few genotype 4 and 6 infections.
Grazoprevir-elbasvir achieved high SVR12 rates in treatment-naive cirrhotic and noncirrhotic patients with genotype 1, 4, or 6 infection. This once-daily, all-oral, fixed-combination regimen represents a potent new therapeutic option for chronic HCV infection.
Merck & Co.
需要新的无干扰素和利巴韦林的治疗方案来治疗丙型肝炎病毒（HCV）感染。
评估格拉瑞韦（NS3/4A 蛋白酶抑制剂）和艾尔巴韦（NS5A 抑制剂）在初治患者中的安全性和疗效。
随机、双盲、安慰剂对照试验。（ClinicalTrials.gov：NCT02105467）。
美国、欧洲、澳大利亚、斯堪的纳维亚和亚洲的 60 个中心。
基因型为 1、4 或 6 的初治、无肝硬化或肝硬化的成年患者。
口服、每日一次、固定剂量的格拉瑞韦 100mg/艾尔巴韦 50mg，持续 12 周，根据纤维化和基因型分层。患者随机分为立即治疗和延迟治疗 3:1。
立即治疗组中在治疗 12 周后 HCV RNA 无法检测到的患者比例（SVR12）；两组的不良反应。
在 421 名参与者中，194 名（46%）为女性，157 名（37%）为非白人，382 名（91%）为基因型 1 感染，92 名（22%）为肝硬化。在 316 名接受立即治疗的患者中，316 例（95%[95%CI，92%至 97%]）达到 SVR12，其中 144 例（92%[CI，86%至 96%]）为基因型 1a，129 例（99%[CI，95%至 100%]）为基因型 1b，18 例（100%[CI，82%至 100%]）为基因型 4，8 例（80%[CI，44%至 98%]）为基因型 6，68 例（97%[CI，90%至 100%]）为肝硬化，231 例（94%[CI，90%至 97%]）为无肝硬化。13 例（4%）患者发生病毒学失败，包括 1 例突破感染和 12 例复发，与基线 NS5A 多态性以及新出现的 NS3 或 NS5A 变异体或两者有关。在活性组和安慰剂组中分别有 9 名（2.8%）和 3 名（2.9%）患者发生严重不良事件（差异<0.05 个百分点[CI，-5.4 至 3.1 个百分点]）；均与药物无关。在活性组中最常见的不良反应是头痛（17%）、疲劳（16%）和恶心（9%）。
该研究缺乏活性对照组，且基因型 4 和 6 感染相对较少。
格拉瑞韦-艾尔巴韦在基因型为 1、4 或 6 的初治肝硬化和非肝硬化患者中达到了很高的 SVR12 率。这种每日一次、口服、固定剂量的联合治疗方案为慢性 HCV 感染提供了一种新的有效治疗选择。
默克公司。
