Telaprevir is Effective Given Every 12 H at 750 Mg with Pegylated Interferon-α2B and Ribavirin to Japanese Patients with HCV-1B Il28B Rs8099917 Tt
Telaprevir is Effective Given Every 12 H at 750 Mg with Pegylated Interferon-α2B and Ribavirin to Japanese Patients with HCV-1B Il28B Rs8099917 Tt
复制标题
对于日本 HCV-1B Il28B Rs8099917 Tt 患者，每 12 小时给予特拉匹韦 750 毫克联合聚乙二醇化干扰素-α2B 和利巴韦林是有效的
作者：
Y. Kawakami;F. Suzuki;Y. Karino;J. Toyota;H. Kumada;K. Chayama
本研究的目的是探讨聚乙二醇化干扰素-α2b （PEG-IFN）和利巴韦林（RBV）三联治疗中，间隔8或12小时给予750 mg特拉匹韦（TVR）治疗慢性HCV感染患者的疗效、安全性和药代动力学。方法将52例预期对治疗有良好反应（rs8099917 TT基因型或既往治疗复发）的HCV基因型1b高病毒载量患者随机分为两组，每隔8小时（q8h）或12小时（q12h）给予750 mg TVR联合PEG-IFN和RBV治疗12周，然后再加用PEG-IFN和RBV治疗12周。该研究的主要终点是治疗结束后12周未检测到HCV RNA（持续病毒学反应[SVR]12）。结果q8h和q12h的SVR12率均为92.3%（24/26）。与q12h相比，q8h的平均log10 HCV RNA水平和病毒反应的变化也相似，而药代动力学特性，如最大血浆浓度、24 h浓度-时间曲线下面积和TVR的血浆谷浓度，在q8h略高于q12h （P < 0.05）。q12h因贫血或肾损害而停药的频率明显高于q8h （6/26 [23%] vs 0/20 [0%]， P=0.02）。结论对于体重较轻的HCV感染患者，特别是既往复发和基因型为rs8099917 TT（干扰素-λ 4 ss469415590多态性TT/TT）基因型的患者，应考虑每隔12 h给予TVR。
Background The aim of this study is to explore the efficacy, safety and pharmacokinetics of 750 mg telaprevir (TVR) given at 8 or 12 h intervals during triple therapy with pegylated interferon-α2b (PEG-IFN) and ribavirin (RBV) for patients with chronic HCV infection. Methods A total of 52 patients with high viral loads of HCV genotype 1b who were expected to respond well to therapy (rs8099917 TT genotype or relapse to previous therapy) were randomly assigned to two groups who were given 750 mg TVR at either 8 h (q8h) or 12 h (q12h) intervals in combination with PEG-IFN and RBV for 12 weeks, followed by 12 additional weeks of treatment with PEG-IFN and RBV alone. The primary end point of the study was undetectable HCV RNA at 12 weeks after the end of treatment (sustained virological response [SVR]12). Results SVR12 rates were 92.3% (24/26) for both q8h and q12h. The changes in mean log10 HCV RNA levels and viral response were also similar in q8h compared to q12h, whereas pharmacokinetic properties such as maximum plasma concentration, area under the concentration-time curve at 24 h and trough plasma concentration of TVR were slightly higher in q8h than in q12h (P>0.2). The frequency of TVR discontinuation due to anaemia or renal damage was significantly higher in q12h than in q8h (6/26 [23%] versus 0/20 [0%], respectively; P=0.02). Conclusions TVR given at 12 h intervals should be considered for patients with lower body weight, especially patients with prior relapse and with IL28B polymorphisms at rs8099917 TT (interferon-λ 4 ss469415590 polymorphism TT/TT) genotype in patients with genotype 1b HCV infection.