Background:
In patients with chronic infection with hepatitis C virus (HCV) genotype 1, treatment with peginterferon alfa and ribavirin for 48 weeks results in rates of sustained virologic response of 40 to 50%. Telaprevir is a specific inhibitor of the HCV serine protease and could be of value in HCV treatment.

Methods:
A total of 334 patients who had chronic infection with HCV genotype 1 and had not been treated previously were randomly assigned to receive one of four treatments involving various combinations of telaprevir (1250mg on day 1, then 750mg every 8 hours), peginterferon alfa-2a (180μg weekly), and ribavirin (dose according to body weight). The T12PR24 group (81 patients) received telaprevir, peginterferon alfa-2a, and ribavirin for 12 weeks, followed by peginterferon alfa-2a and ribavirin for 12 more weeks. The T12PR12 group (82 patients) received telaprevir, peginterferon alfa-2a, and ribavirin for 12 weeks. The T12P12 group (78 patients) received telaprevir and peginterferon alfa-2a without ribavirin for 12 weeks. The PR48 (control) group (82 patients) received peginterferon alfa-2a and ribavirin for 48 weeks. The primary end point, a sustained virologic response (an undetectable HCV RNA level 24 weeks after the end of therapy), was compared between the control group and the combined T12P12 and T12PR12 groups.

Results:
The rate of sustained virologic response for the T12PR12 and T12P12 groups combined was 48% (77 of 160 patients), as compared with 46% (38 of 82) in the PR48 (control) group (P=0.89). The rate was 60% (49 of 82 patients) in the T12PR12 group (P=0.12 for the comparison with the PR48 group), as compared with 36% (28 of 78 patients) in the T12P12 group (P=0.003; P=0.20 for the comparison with the PR48 group). The rate was significantly higher in the T12PR24 group (69% [56 of 81 patients]) than in the PR48 group (P=0.004). The adverse events with increased frequency in the telaprevir-based groups were pruritus, rash, and anemia.

Conclusions:
In this phase 2 study of patients infected with HCV genotype 1 who had not been treated previously, one of the three telaprevir groups had a significantly higher rate of sustained virologic response than that with standard therapy. Response rates were lowest with the regimen that did not include ribavirin. (ClinicalTrials.gov number, NCT00372385.)

研究表明Telaprevir为丙肝患者带来新希望

近日，强生及Vertex两家公司公布了Telaprevir+抗丙肝标准药疗法的最新临床实验数据，实验结果显示，很多难治性丙肝患者采用这种疗法后能够治愈。
该实验名为PROVE3，所得数据已发表在《新英格兰医学杂志》当中。数据证实，与目前的标准药相比，之前接受过治疗但失败的患者转用Telaprevir基疗法后效果更好，在持续性病毒反应（SVR）方面达到预期，即患者完成治疗6个月后，通过血液检查未检测到病毒，这意味着疾病已经治愈。
目前，治疗丙肝的标准药物为聚乙二醇干扰素+病毒唑，但这种疗法具有副作用，而且那些1基因型丙肝患者首次采用上述疗法后只有半数的人能治愈。PROVE3研究人员表示，通常情况下，首次用药后在SVR方面未达到预定效果的患者即使再度用药也难以痊愈，而这次临床实验则证实Telaprevir有可能会给他们带来新的希望。