Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study
Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study
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DOI：
10.1016/s0140-6736(14)61036-9
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发表时间：
2014-11-15
期刊：
影响因子：
168.9
通讯作者：
Jacobson, Ira M.
中科院分区：
文献类型：
--
作者：
Lawitz, Eric;Sulkowski, Mark S.;Jacobson, Ira M.
背景丙型肝炎病毒（HCV）感染需要无干扰素治疗。我们调查了simeprevir和sofosbuvir.Methods相结合的疗效，我们招募了慢性HCV基因型1感染的患者，以前没有反应的聚乙二醇干扰素（聚乙二醇干扰素）和利巴韦林或治疗幼稚。患者以2：1：2：1的比例被随机分配到两个队列中，每天接受150 mg Simeprevir和400 mg索非布韦，持续24周（第1组）或不接受（第2组）利巴韦林，或持续12周（第3组）或不接受（第4组）利巴韦林：METAVIR评分F0-F2的既往无应答者（队列1）和METAVIR评分F3-F4的既往无应答者和初治患者（队列2）。主要终点是停止治疗后12周的持续病毒学应答（SVR 12）。按意向治疗进行分析。将队列1和队列2的安全性数据汇总进行分析。本研究已在ClinicalTrials注册。结果168例患者入组并随机分配，167例开始治疗（队列1中n=80，队列2中n=87）。154例（92%）患者实现了SVR 12（队列1中n=72 [90%，95%CI 81-96]，队列2中n=82 [94%，87-98]）。合并组中最常见的不良事件为疲乏（n=52 [31%]）、头痛（n=33 [20%]）和恶心（n=26 [16%]）。第1组和第3组各有1/54例患者（2%）发生4级不良事件，第2组有3/31例患者（10%）发生4级不良事件，而除血淀粉酶浓度升高外，所有患者中不到5%报告了3-4级不良事件。在4例（2%）患者中观察到严重不良事件，均在第1组和第2组中。4例（2%）患者因不良事件而停止所有研究治疗，其中3例在第12周前停止。解释simeprevir和sofosbuvir联合治疗有效且耐受性良好。
Background Interferon-free regimens are needed to treat hepatitis C virus (HCV) infections. We investigated the efficacy of combined simeprevir and sofosbuvir.Methods We enrolled patients with chronic HCV genotype 1 infections who had previously not responded to pegylated interferon (peginterferon) and ribavirin or were treatment naive. Patients were randomly assigned in a 2: 1: 2: 1 ratio to receive 150 mg simeprevir and 400 mg sofosbuvir daily for 24 weeks with (group 1) or without (group 2) ribavirin or for 12 weeks with (group 3) or without (group 4) ribavirin, in two cohorts: previous non-responders with METAVIR scores F0-F2 (cohort 1) and previous non-responders and treatment-naive patients with METAVIR scores F3-F4 (cohort 2). The primary endpoint was sustained virological response 12 weeks after stopping treatment (SVR12). Analysis was done by intention to treat. Safety data from cohorts 1 and 2 were pooled for analysis. This study is registered with ClinicalTrials. gov, number NCT01466790.Findings 168 patients were enrolled and randomised, and 167 started treatment (n=80 in cohort 1 and n=87 in cohort 2). SVR12 was achieved in 154 (92%) patients (n=72 [90%, 95% CI 81-96] in cohort 1 and n=82 [94%, 87-98] in cohort 2). The most common adverse events in the pooled groups were fatigue (n=52 [31%]), headache (n=33 [20%]), and nausea (n=26 [16%]). Grade 4 adverse events were seen in one (2%) of 54 patients in each of groups 1 and 3 and in three (10%) of 31 patients in group 2, whereas grade 3-4 events were reported in less than 5% of all patients, except increased blood amylase concentration. Serious adverse events were seen in four (2%) patients, all in groups 1 and 2. Four (2%) patients discontinued all study treatment because of adverse events, three before week 12.Interpretation Combined simeprevir and sofosbuvir was efficacious and well tolerated.