Kao Jia-Horng, Chien Rong-Nan, Chang Ting-Tsung, Peng Cheng-Yuan, Hu Tsung-Hui, Lo Gin-Ho, Wang Horng-Yuan, Chen Jyh-Jou, Yang Jenny C, Knox Steven J, Han Lingling, Mo Hongmei, Mathias Anita, Brainard Diana M, Sheen I-Shyan, Hsu Yu-Chun, Chu Chi-Jen, Chuang Wan-Long
National Taiwan University College of Medicine and Hospital, Taipei, Taiwan.
Liver Research Unit, Chang Gung Memorial Hospital-Keelung, Keelung, Taiwan.
Liver Int. 2016 Aug;36(8):1101-7. doi: 10.1111/liv.13082. Epub 2016 Mar 23.
BACKGROUND & AIMS: In Taiwan, patients with chronic hepatitis C virus (HCV) infection are currently treated with pegylated interferon-alpha plus ribavirin, but interferon-based regimens can be poorly tolerated, especially by those with advanced liver disease and the elderly. Sofosbuvir, an oral nucleotide analogue inhibitor of HCV NS5B polymerase, is approved in Europe, the USA and Japan for treating chronic HCV infection. This phase 3b study examined the efficacy and safety of sofosbuvir plus ribavirin in Taiwanese patients with chronic genotype 2 HCV infection ± compensated cirrhosis.
In this multicentre, open-label, phase 3b (NCT02021643) study, 87 patients (n = 43, treatment-naive; n = 44, treatment-experienced) received 12 weeks of treatment with sofosbuvir plus weight-based ribavirin. The primary efficacy endpoint was the proportion of patients with sustained virological response 12 weeks after treatment discontinuation (SVR12). Safety and pharmacokinetic data were also collected.
All 87 patients (100%; 95% confidence interval, 92-100%) achieved SVR12, including the 13 patients with compensated cirrhosis. The most common treatment-emergent adverse events (AEs) were insomnia (16%, 14/87) and upper respiratory tract infection (16%, 14/87). No grade 3 or grade 4 AE was reported. There was one serious AE (biliary colic), which was deemed unrelated to study treatment. Laboratory abnormalities other than ribavirin-related reductions in haemoglobin were uncommon.
The results from this phase 3b study demonstrate that 12 weeks of treatment with the interferon-free regimen sofosbuvir plus ribavirin is effective and well tolerated in both treatment-naive and treatment-experienced Taiwanese patients with chronic genotype 2 HCV infection.
在台湾,慢性丙型肝炎病毒(HCV)感染患者目前接受聚乙二醇化干扰素-α联合利巴韦林治疗,但基于干扰素的治疗方案耐受性较差,尤其是晚期肝病患者和老年人。索磷布韦是一种口服的HCV NS5B聚合酶核苷酸类似物抑制剂,在欧洲、美国和日本已被批准用于治疗慢性HCV感染。这项3b期研究考察了索磷布韦联合利巴韦林治疗台湾慢性2型HCV感染合并或不合并代偿期肝硬化患者的疗效和安全性。
在这项多中心、开放标签的3b期(NCT02021643)研究中,87例患者(43例初治患者;44例经治患者)接受了12周的索磷布韦联合基于体重的利巴韦林治疗。主要疗效终点是停药12周后持续病毒学应答(SVR12)患者的比例。同时收集安全性和药代动力学数据。
所有87例患者(100%;95%置信区间,92-100%)均达到SVR12,包括13例代偿期肝硬化患者。最常见的治疗中出现的不良事件(AE)是失眠(16%,14/87)和上呼吸道感染(16%,14/87)。未报告3级或4级AE。有1例严重AE(胆绞痛),被认为与研究治疗无关。除了与利巴韦林相关的血红蛋白降低外,实验室异常并不常见。
这项3b期研究结果表明,对于台湾初治和经治的慢性2型HCV感染患者,使用不含干扰素的方案索磷布韦联合利巴韦林治疗12周有效且耐受性良好。