Once-daily simeprevir (TMC435) with peginterferon/ribavirin for treatment-naive hepatitis C genotype 1-infected patients in Japan: the DRAGON study
Once-daily simeprevir (TMC435) with peginterferon/ribavirin for treatment-naive hepatitis C genotype 1-infected patients in Japan: the DRAGON study
复制标题
DOI：
10.1007/s00535-013-0875-1
复制
发表时间：
2014-01-01
影响因子：
6.3
通讯作者：
Goto, Shoichiro
中科院分区：
文献类型：
--
作者：
Hayashi, Norio;Seto, Chiharu;Goto, Shoichiro
背景：在日本的一项多中心随机临床试验中，92例患者接受西美普韦(50或100 mg，qd)治疗12周或48周(根据应答引导治疗[RGT]标准)，评价了西美普韦(TMC435)的有效性、安全性和药代动力学。西美普韦是一种每日一次的非共价口服丙型肝炎病毒NS3/4A蛋白酶抑制剂，与聚乙二醇干扰素α-2a/利巴韦林(PEGIFNα-2a/RBV)联合治疗24周或48周。结果与PR48组相比，西美普韦组血浆中丙型肝炎病毒核糖核酸下降迅速且更为显著(西美普韦50 mg组、100 mg组和PR48组第4周分别为-5.2、-5.2和-2.9log(10)IU/mL)。高快速病毒学应答率(西美普韦50 mg组、100 mg联合组和PR48组分别为83、90和8%)导致高持续病毒学应答率(77-92%，而PR48组为46%)。除了一名患者外，所有接受西美普韦治疗的患者都有资格在24周后完成治疗(RGT)。接受西美普韦治疗的患者复发率很低(8-17%，而PR48组为36%)。西美普韦与PR48组的安全性无显著差异。结论在日本丙型肝炎病毒1型感染的初治患者中，与单独使用西美普韦相比，西美普韦qd加入PegIFNα-2a/RBV具有较强的抗病毒活性，显著提高了持续病毒学应答率，缩短了24周的治疗时间。西美普韦总体上是安全的，耐受性良好。(ClinicalTrials.gov编号，NCT00996476)。
Background Efficacy, safety and pharmacokinetics of simeprevir (TMC435), a once-daily, noncovalent, oral hepatitis C virus (HCV) NS3/4A protease inhibitor, was evaluated in combination with peginterferon alpha-2a/ribavirin (PegIFN alpha-2a/RBV) for treatment-naive, HCV genotype 1-infected patients in Japan.Methods In a multicenter, randomized clinical trial in Japan, ninety-two patients received either simeprevir (50 or 100 mg QD) for 12 or 24 weeks with PegIFN alpha-2a/RBV for 24 or 48 weeks (according to response-guided therapy [RGT] criteria), or PegIFN alpha-2a/RBV for 48 weeks (PR48 group).Results Compared with the PR48 group, plasma HCV RNA reductions in the simeprevir groups were rapid and more substantial (Week 4: -5.2,-5.2 and -2.9 log(10)IU/mL for simeprevir 50 mg combined, 100 mg combined, and PR48 groups, respectively). High rapid virologic response rates (83, 90, and 8 % for simeprevir 50 mg combined, 100 mg combined, and PR48 groups, respectively) led to high sustained virologic response rates (77-92 %, compared with 46 % for PR48). All but one of the simeprevir-treated patients were eligible to complete treatment after 24 weeks (RGT). Relapse rates in simeprevir-treated patients were low (8-17 %, compared with 36 % for the PR48 group). There were no notable differences in the safety profile between the simeprevir and PR48 groups.Conclusions The addition of simeprevir QD to PegIFN alpha-2a/RBV, as compared with PegIFN alpha-2a/RBV alone, demonstrated potent antiviral activity and significantly improved the rates of sustained virologic response, with a shortened 24-week treatment duration, in treatment-naive patients infected with HCV genotype 1 in Japan. Simeprevir was generally safe and well tolerated.(ClinicalTrials.gov number, NCT00996476).