Hepatology and Liver Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Hepatology. 2010 Oct;52(4):1208-15. doi: 10.1002/hep.23827.
Ribavirin-induced hemolytic anemia can prompt dose reductions and lower sustained virologic response (SVR) rates in the treatment of patients with chronic hepatitis C. The study aimed to determine if weight-based dosing of taribavirin (TBV), an oral prodrug of ribavirin (RBV), demonstrated efficacy comparable to RBV while maintaining its previously demonstrated anemia advantage with fixed dose administration. A U.S. phase 2b randomized, open-label, active-controlled, parallel-group study was conducted in 278 treatment-naive patients infected with genotype 1 who were stratified by body weight and baseline viral load. Patients were randomized 1:1:1:1 to receive TBV (20, 25, or 30 mg/kg/day) or RBV (800-1400 mg/day) with pegylated interferon alfa-2b for 48 weeks. The SVR rates in this difficult-to-cure patient demographics (mean age, 49 years; 61% male; 30% African American or Latino; high viral load; advanced fibrosis; and mean weight, 82 kg) were 28.4%, 24.3%, 20.6%, and 21.4% in the 20, 25, and 30 mg/kg TBV groups and the RBV group, respectively. There were no statistical differences in the efficacy analyses. Anemia rates were significantly lower (P < 0.05) in the 20 and 25 mg/kg/day TBV treatment groups (13.4% and 15.7%, respectively) compared to RBV (32.9%). The most common adverse events in all groups were fatigue, diarrhea, and insomnia. Diarrhea, reported in 38% of TBV patients versus 21% of RBV patients, was generally mild and not dose-limiting.
All TBV doses demonstrated efficacy and tolerability comparable to that of RBV; however, the 25 mg/kg dose demonstrated the optimal balance of safety and efficacy. Anemia rates were significantly lower for TBV given at 20-25 mg/kg than RBV. These data suggest weight-based dosing with TBV provides a safe and effective treatment alternative to RBV for chronic hepatitis C. American Association for the Study of Liver Diseases.
利巴韦林诱导的溶血性贫血可导致慢性丙型肝炎患者治疗时剂量减少和持续病毒学应答（SVR）率降低。本研究旨在确定利巴韦林（RBV）前体药物替比夫定（TBV）的体重剂量是否能与 RBV 一样有效，同时保持其固定剂量给药时已证明的贫血优势。在美国进行了一项 2b 期随机、开放标签、活性对照、平行组研究，共纳入 278 例未经治疗的基因型 1 感染患者，根据体重和基线病毒载量进行分层。患者按 1:1:1:1 随机分为 TBV（20、25 或 30mg/kg/天）或 RBV（800-1400mg/天）与聚乙二醇干扰素 alfa-2b 联合治疗 48 周。在这一难以治愈的患者人群（平均年龄 49 岁；61%为男性；30%为非裔美国人或拉丁裔；高病毒载量；晚期纤维化；平均体重 82kg）中，20、25 和 30mg/kgTBV 组和 RBV 组的 SVR 率分别为 28.4%、24.3%、20.6%和 21.4%。疗效分析无统计学差异。TBV 治疗组的贫血发生率明显低于 RBV 组（分别为 13.4%和 15.7%，P<0.05）。所有组中最常见的不良反应为疲劳、腹泻和失眠。TBV 组的腹泻发生率为 38%，而 RBV 组为 21%，通常为轻度且非剂量限制。
所有 TBV 剂量均显示出与 RBV 相当的疗效和耐受性；然而，25mg/kg 剂量显示出最佳的安全性和疗效平衡。TBV 20-25mg/kg 组的贫血发生率明显低于 RBV 组。这些数据表明，TBV 的体重剂量为慢性丙型肝炎提供了一种安全有效的 RBV 治疗替代方案。美国肝病研究协会。
