Telaprevir for Previously Untreated Chronic Hepatitis C Virus Infection
Telaprevir for Previously Untreated Chronic Hepatitis C Virus Infection
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DOI：
10.1056/nejmoa1012912
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发表时间：
2011-06-23
影响因子：
158.5
通讯作者：
Zeuzem, Stefan
中科院分区：
文献类型：
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作者：
Jacobson, Ira M.;McHutchison, John G.;Zeuzem, Stefan
背景在2期临床试验中，特拉匹韦，一种丙型肝炎病毒（HCV）基因型1蛋白酶抑制剂，与聚乙二醇干扰素-利巴韦林联合，与聚乙二醇干扰素-利巴韦林单独相比，显示出改善的疗效，并有可能缩短大多数患者的治疗持续时间。我们将1088例HCV基因型1感染且既往未接受过感染治疗的患者分为三组：a组接受特拉匹韦联合聚乙二醇干扰素α-2a和利巴韦林治疗12周（T12 PR组），如果在第4周和第12周HCV RNA检测不到，则单独使用聚乙二醇干扰素-利巴韦林12周，如果在任一时间点HCV RNA检测到，则单独使用聚乙二醇干扰素-利巴韦林36周; a组接受特拉匹韦与聚乙二醇干扰素-利巴韦林联合治疗8周，安慰剂与聚乙二醇干扰素-利巴韦林联合治疗4周（T8 PR组），随后在相同的HCV RNA标准基础上给予聚乙二醇干扰素-利巴韦林治疗12或36周;或接受安慰剂与聚乙二醇干扰素-利巴韦林治疗12周，随后接受聚乙二醇干扰素-利巴韦林治疗36周（PR组）。主要终点是末次计划剂量研究治疗后24周血浆HCV RNA检测不到的患者比例（持续病毒学应答）。
BackgroundIn phase 2 trials, telaprevir, a hepatitis C virus (HCV) genotype 1 protease inhibitor, in combination with peginterferon-ribavirin, as compared with peginterferon-ribavirin alone, has shown improved efficacy, with potential for shortening the duration of treatment in a majority of patients.MethodsIn this international, phase 3, randomized, double-blind, placebo-controlled trial, we assigned 1088 patients with HCV genotype 1 infection who had not received previous treatment for the infection to one of three groups: a group receiving telaprevir combined with peginterferon alfa-2a and ribavirin for 12 weeks (T12PR group), followed by peginterferon-ribavirin alone for 12 weeks if HCV RNA was undetectable at weeks 4 and 12 or for 36 weeks if HCV RNA was detectable at either time point; a group receiving telaprevir with peginterferon-ribavirin for 8 weeks and placebo with peginterferon-ribavirin for 4 weeks (T8PR group), followed by 12 or 36 weeks of peginterferon-ribavirin on the basis of the same HCV RNA criteria; or a group receiving placebo with peginterferon-ribavirin for 12 weeks, followed by 36 weeks of peginterferon-ribavirin (PR group). The primary end point was the proportion of patients who had undetectable plasma HCV RNA 24 weeks after the last planned dose of study treatment (sustained virologic response).ResultsSignificantly more patients in the T12PR or T8PR group than in the PR group had a sustained virologic response (75% and 69%, respectively, vs. 44%; P