Hadassah Medical Center, Jerusalem, Israel.
Liver Int. 2011 May;31(5):667-75. doi: 10.1111/j.1478-3231.2010.02360.x. Epub 2010 Oct 29.
Telbivudine showed greater antiviral suppression than lamivudine in phase II and III clinical trials.
The present phase IIIb, randomized, double-blind, multicentre global trial assessed the antiviral efficacy and safety of telbivudine switch in chronic hepatitis B (CHB) patients who exhibited persistent viraemia under lamivudine therapy.
HBeAg-positive and HBeAg-negative adult patients (N=246) with persistent viraemia [hepatitis B virus (HBV) DNA>3 log(10) copies/ml] under lamivudine treatment for 12-52 weeks were randomized (1:1) to continue lamivudine 100 mg/day or switch to telbivudine 600 mg/day for 1 year. Primary endpoint was the reduction in serum HBV DNA levels from baseline at Week 24.
The mean reduction in serum HBV DNA levels from baseline with telbivudine was significantly higher than lamivudine at Week 24 (-1.9 ± 0.18 vs. -0.9 ± 0.27 log(10) copies/ml; P<0.001) and maintained through 1 year. The rate of treatment failure was significantly lower (P<0.001) for patients who switched to telbivudine (5%) compared with those who continued lamivudine (20%) after 52 weeks of treatment. In the telbivudine group, treatment failure occurred in only five patients with >24 weeks of prior lamivudine treatment, all associated with pre-existent lamivudine-resistant mutations. Genotypic resistance rates were higher in patients continuing lamivudine compared with those who switched to telbivudine with <24 weeks of lamivudine exposure. Both treatments were well tolerated with similar safety profiles.
Early (≤ 24 weeks) switch to telbivudine improves virological outcomes in CHB patients with persistent viral replication under lamivudine treatment.
替比夫定在 II 期和 III 期临床试验中显示出比拉米夫定更强的抗病毒抑制作用。
本 IIIb 期、随机、双盲、多中心全球试验评估了替比夫定在接受拉米夫定治疗 12-52 周后持续病毒血症的慢性乙型肝炎（CHB）患者中的抗病毒疗效和安全性。
HBeAg 阳性和 HBeAg 阴性成年患者（N=246），在拉米夫定治疗 12-52 周后持续病毒血症[乙型肝炎病毒（HBV）DNA>3 log(10) 拷贝/ml]，随机（1:1）分为继续拉米夫定 100 mg/天或换用替比夫定 600 mg/天治疗 1 年。主要终点是从基线到第 24 周时血清 HBV DNA 水平的降低。
替比夫定组从基线开始的血清 HBV DNA 水平平均降低显著高于拉米夫定组（-1.9±0.18 与-0.9±0.27 log(10) 拷贝/ml；P<0.001），并持续到 1 年。与继续拉米夫定组（20%）相比，换用替比夫定组（5%）的治疗失败率显著降低（P<0.001），治疗 52 周后。在替比夫定组中，仅有 5 例在拉米夫定治疗>24 周后发生治疗失败，均与预先存在的拉米夫定耐药突变相关。在拉米夫定暴露时间<24 周时换用替比夫定的患者中，基因型耐药率高于继续拉米夫定的患者。两种治疗方法均耐受良好，安全性相似。
在拉米夫定治疗持续病毒复制的 CHB 患者中，早期（≤24 周）换用替比夫定可改善病毒学结果。
