Wingate University, Wingate, North Carolina, USA.
Ann Pharmacother. 2011 May;45(5):639-48. doi: 10.1345/aph.1P430. Epub 2011 May 10.
To review the use of telaprevir for the treatment of chronic hepatitis C.
Clinical studies were identified through MEDLINE (1966-January 2011), bibliographies of articles, clinicaltrials.gov, and fda.gov, using key words VX-950, telaprevir, and chronic hepatitis C.
Phase 1, 2, and 3 human and animal studies describing the pharmacology, pharmacokinetics, efficacy, and safety of telaprevir were identified. Additional articles were identified from the bibliographies of articles retrieved through MEDLINE.
Telaprevir is an NS3/4A protease inhibitor under investigation for the treatment of chronic hepatitis C virus (HCV) with pegylated interferon and ribavirin. Telaprevir competes with viral peptide substrates for the active site of NS3 and inhibits NS3-NS4A protease activity. Telaprevir has activity against HCV genotype 1 infection in vitro and in vivo, but monotherapy results in rapid viral resistance. In 3 Phase 2 and 3 Phase 3 randomized placebo-controlled trials, 12 weeks of telaprevir, along with varying durations of ribavirin treatment, induced higher sustained virologic response (SVR) compared with ribavirin alone. SVR was approximately 70% in treatment-naïve patients, 50-60% for patients in whom SVR had not occurred with prior ribavirin treatment, and 40-45% of those who received ribavirin alone. There was a high incidence of maculopapular rash (52% in 1 trial) and anemia (27% in 1 trial) in telaprevir-treated patients. The average dropout rate in Phase 3 trials as a result of adverse effects was 13%.
Twelve weeks of telaprevir with concomitant ribavirin treatment increases SVR for treatment-naïve and non-naïve patients with genotype 1 chronic HCV compared to 48 weeks of ribavirin treatment. Telaprevir may shorten the length of ribavirin therapy for some patients with extended rapid viral response, but viral mutations, adverse effects, and a high dropout rate may reduce the SVR seen in clinical practice.
回顾替拉瑞韦治疗慢性丙型肝炎的应用。
通过 MEDLINE（1966 年-2011 年 1 月）、文章参考文献、clinicaltrials.gov 和 fda.gov 检索临床研究，使用关键词 VX-950、替拉瑞韦和慢性丙型肝炎。
鉴定了描述替拉瑞韦的药理学、药代动力学、疗效和安全性的 1 期、2 期和 3 期人体和动物研究。从通过 MEDLINE 检索到的文章参考文献中鉴定了其他文章。
替拉瑞韦是一种正在研究用于治疗聚乙二醇干扰素和利巴韦林治疗慢性丙型肝炎病毒（HCV）的 NS3/4A 蛋白酶抑制剂。替拉瑞韦与病毒肽底物竞争 NS3 的活性部位并抑制 NS3-NS4A 蛋白酶活性。替拉瑞韦在体外和体内对 HCV 基因型 1 感染具有活性，但单药治疗会迅速产生病毒耐药性。在 3 项 2 期和 3 项 3 期随机安慰剂对照试验中，替拉瑞韦与利巴韦林治疗持续 12 周，与单独使用利巴韦林相比，诱导更高的持续病毒学应答（SVR）。在未经治疗的患者中，SVR 约为 70%，在先前利巴韦林治疗未发生 SVR 的患者中为 50-60%，在单独接受利巴韦林治疗的患者中为 40-45%。替拉瑞韦治疗患者中皮疹（1 项试验中为 52%）和贫血（1 项试验中为 27%）的发生率较高。由于不良反应，3 期试验的平均退出率为 13%。
替拉瑞韦联合利巴韦林治疗 12 周可提高基因型 1 慢性 HCV 治疗初治和非初治患者的 SVR，与利巴韦林治疗 48 周相比。替拉瑞韦可能会缩短某些快速病毒应答延长患者的利巴韦林治疗时间，但病毒突变、不良反应和高退出率可能会降低临床实践中观察到的 SVR。
