Suzuki Fumitaka, Toyota Joji, Ikeda Kenji, Chayama Kazuaki, Mochida Satoshi, Hayashi Norio, Ishikawa Hiroki, Miyagoshi Hidetaka, Hu Wenhua, McPhee Fiona, Hughes Eric A, Kumada Hiromitsu
Toranomon Hospital, Tokyo, Japan.
Antivir Ther. 2014;19(5):491-9. doi: 10.3851/IMP2730. Epub 2014 Jan 22.
Daclatasvir-containing regimens have the potential to address limitations of current regimens combining peginterferon alfa and ribavirin with first-generation protease inhibitors for treatment of chronic HCV genotype 1 infection.
In this randomized, double-blind study, 27 Japanese treatment-naive patients received once-daily daclatasvir 10 mg or 60 mg or placebo, each combined with peginterferon alfa-2b/ribavirin; 18 prior null (n=9) or partial (n=9) responders received the same daclatasvir-containing regimens without a placebo arm. Daclatasvir recipients with protocol-defined response (HCV RNA<15 IU/ml at week 4, undetectable at week 12) were treated for 24 weeks; those without protocol-defined response and placebo recipients continued treatment to week 48.
Sustained virological response 24 weeks post-treatment (SVR24) was achieved by 66.7%, 90.0% and 62.5% of treatment-naive patients in the daclatasvir 10 mg, 60 mg and placebo groups, respectively. Prior non-responders had more frequent virological failure; 22.2% and 33.3% of daclatasvir 10 mg and 60 mg recipients, respectively, achieved SVR24. Adverse events were similar across groups and were typical of peginterferon alfa-2b/ribavirin. Pyrexia, headache, alopecia, decreased appetite and malaise were the most common adverse events; two daclatasvir recipients discontinued due to adverse events.
Daclatasvir 60 mg combined with peginterferon alfa-2b and ribavirin achieved a high rate of SVR24 in treatment-naive patients with HCV genotype 1 infection, with tolerability similar to that of peginterferon alfa-2b/ribavirin alone. However, regimens with greater antiviral potency are needed for prior non-responders.
含达卡他韦的治疗方案有可能解决目前聚乙二醇干扰素α与利巴韦林联合第一代蛋白酶抑制剂治疗慢性丙型肝炎1型感染方案的局限性。
在这项随机、双盲研究中，27例初治的日本患者每日一次接受10mg或60mg达卡他韦或安慰剂治疗，每种治疗均联合聚乙二醇干扰素α-2b/利巴韦林；18例既往无应答（n = 9）或部分应答（n = 9）者接受相同的含达卡他韦治疗方案，无安慰剂组。符合方案定义的应答（第4周时HCV RNA<15 IU/ml，第12周时检测不到）的达卡他韦接受者治疗24周；不符合方案定义的应答者和安慰剂接受者继续治疗至48周。
治疗24周后持续病毒学应答（SVR24）率在达卡他韦10mg组、60mg组和安慰剂组的初治患者中分别为66.7%、90.0%和62.5%。既往无应答者病毒学失败更频繁；达卡他韦10mg组和60mg组分别有22.2%和33.3%的接受者实现SVR24。各治疗组不良事件相似，且是聚乙二醇干扰素α-2b/利巴韦林的典型不良事件。发热、头痛、脱发、食欲减退和不适是最常见的不良事件；两名达卡他韦接受者因不良事件停药。
60mg达卡他韦联合聚乙二醇干扰素α-2b和利巴韦林在初治的丙型肝炎1型感染患者中实现了较高的SVR24率，耐受性与单独使用聚乙二醇干扰素α-2b/利巴韦林相似。然而，既往无应答者需要抗病毒效力更强的治疗方案。
