Duke Clinical Research Institute and Duke University Medical Center, Durham, NC, USA.
N Engl J Med. 2010 Apr 8;362(14):1292-303. doi: 10.1056/NEJMoa0908014.
Patients with genotype 1 hepatitis C virus (HCV) who do not have a sustained response to therapy with peginterferon alfa and ribavirin have a low likelihood of success with retreatment.
We randomly assigned patients with HCV genotype 1 who had not had a sustained virologic response after peginterferon alfa-ribavirin therapy to one of four treatment groups: 115 patients to the T12PR24 group, receiving telaprevir (1125-mg loading dose, then 750 mg every 8 hours) for 12 weeks and peginterferon alfa-2a (180 microg per week) and ribavirin (1000 or 1200 mg per day, according to body weight) for 24 weeks; 113 patients to the T24PR48 group, receiving telaprevir for 24 weeks and peginterferon alfa-2a and ribavirin for 48 weeks (at the same doses as in the T12PR24 group); 111 patients to the T24P24 group, receiving telaprevir and peginterferon alfa-2a for 24 weeks (at the same doses as in the T12PR24 group); and 114 patients to the PR48 (or control) group, receiving peginterferon alfa-2a and ribavirin for 48 weeks (at the same doses as in the T12PR24 group). The primary end point was sustained virologic response (undetectable HCV RNA levels 24 weeks after the last dose of study drugs).
The rates of sustained virologic response in the three telaprevir groups--51% in the T12PR24 group, 53% in the T24PR48 group, and 24% in the T24P24 group--were significantly higher than the rate in the control group (14%; P<0.001, P<0.001, and P=0.02, respectively). Response rates were higher among patients who had previously had relapses than among nonresponders. One of the most common adverse events in the telaprevir groups was rash (overall, occurring in 51% of patients, with severe rash in 5%). Discontinuation of study drugs because of adverse events was more frequent in the telaprevir groups than in the control group (15% vs. 4%).
In HCV-infected patients in whom initial peginterferon alfa and ribavirin treatment failed, retreatment with telaprevir in combination with peginterferon alfa-2a and ribavirin was more effective than retreatment with peginterferon alfa-2a and ribavirin alone. (ClinicalTrials.gov number, NCT00420784.)
对聚乙二醇干扰素α和利巴韦林治疗无持续病毒学应答的基因型 1 丙型肝炎病毒（HCV）患者，再次治疗成功的可能性较低。
我们将未对聚乙二醇干扰素α-利巴韦林治疗有持续病毒学应答的 HCV 基因型 1 患者随机分配至 4 个治疗组之一：115 例患者进入 T12PR24 组，接受替拉瑞韦（负荷剂量 1125mg，随后每 8 小时 750mg）治疗 12 周，同时接受聚乙二醇干扰素 alfa-2a（每周 180μg）和利巴韦林（根据体重，每天 1000 或 1200mg）治疗 24 周；113 例患者进入 T24PR48 组，接受替拉瑞韦治疗 24 周，同时接受聚乙二醇干扰素 alfa-2a 和利巴韦林治疗 48 周（剂量与 T12PR24 组相同）；111 例患者进入 T24P24 组，接受替拉瑞韦和聚乙二醇干扰素 alfa-2a 治疗 24 周（剂量与 T12PR24 组相同）；114 例患者进入 PR48（或对照组）组，接受聚乙二醇干扰素 alfa-2a 和利巴韦林治疗 48 周（剂量与 T12PR24 组相同）。主要终点是持续病毒学应答（治疗结束后 24 周 HCV RNA 水平不可检测）。
T12PR24 组、T24PR48 组和 T24P24 组的持续病毒学应答率分别为 51%、53%和 24%，显著高于对照组的 14%（P<0.001，P<0.001 和 P=0.02）。与无应答者相比，先前有复发的患者的应答率更高。替拉瑞韦组最常见的不良反应之一是皮疹（总体发生率为 51%，严重皮疹为 5%）。与对照组相比，替拉瑞韦组因不良反应而停药的发生率更高（15% vs. 4%）。
在初始聚乙二醇干扰素α和利巴韦林治疗失败的 HCV 感染患者中，与单独使用聚乙二醇干扰素 alfa-2a 和利巴韦林相比，用替拉瑞韦联合聚乙二醇干扰素 alfa-2a 和利巴韦林进行再次治疗更有效。（临床试验.gov 编号，NCT00420784）。
