【摘要】 目的:比较聚乙二醇胸腺素α1(PEG-Tα1)联合阿德福韦酯和单用阿德福韦酯治疗HBe Ag阳性慢性乙型肝炎的有效性和安全性,并从药效动力学角度探讨PEG-Tα1的作用机制。方法:采用多中心、随机、双盲、伴有基础治疗的安慰剂平行对照试验方法,共随机入选病例116例,分为试验组或对照组。试验组给药方案为PEG-Tα1(1.6 mg/m L,q.w.)+口服阿德福韦酯胶囊(10 mg,q.d.);对照组给药方案为PEG-Tα1模拟药(1 m L,q.w.)+口服阿德福韦酯胶囊(10 mg,q.d.),自阿德福韦酯第1次给药后第48周揭盲并进行统计分析。主要疗效指标为治疗48周时血清HBe Ag转阴率,次要疗效指标包括血清学、病毒学和生化学指标,并评价药效动力学指标。结果:治疗48周时血清HBe Ag转阴率,试验组为14.29%,对照组为8.93%。试验组较对照组有增加的趋势,但两组间差异无统计学的意义(P=0.5567)。次要疗效指标两组间差异也不具备统计学意义(P>0.05)。药效动力学指标中,试验组在用药4周和24周的血CD3+、CD4+及CD8+T细胞绝对计数显示逐渐增加,在24周达到高峰,对照组在用药前后未见明显变化,但两组间差异无统计学意义(P>0.05)。结论:聚乙二醇胸腺素α1联合阿德福韦酯治疗HBeAg阳性慢性乙肝有较好的安全性,能增强细胞免疫反应,但其有效性尚需通过进一步的大样本量的Ⅲ期临床研究进行证明。更多还原

【Abstract】 Objective: The trial is to evaluate the efficacy and safety of PEG-Tα1 combined adefovir dipivoxil therapy in patients with HBe Ag-positive chronic hepatitis B comparing with adefovir dipivoxil alone,and investigate the pharmacodynamic mechanisms of PEGTα1. Methods: This study was a multi-centre,randomized,double-blind and placebo with basic therapy controlled clinical trial. 116 CHB patients were randomized and assigned in group A( PEG-Tα1 1. 6 mg / m L,q. w.,24 weeks + adefovir dipivoxil capsule 10 mg,q. d.,48 weeks) or( PEG-Tα1 placebo 1 m L,q. w.,24 weeks + adefovir dipivoxil capsule 10 mg,q. d.,48 weeks). Statistical analysis was performed at the end of the 48 th week. The primary efficacy endpoint was the loss of HBe Ag at 48 weeks,and the secondary endpoints included laboratory indexesabout serology,virology and biochemisty. Pharmocodynamic parameters were also analyzed. Results:The loss of HBe Ag at 48 weeks in group A was 14. 29%( 8 /56),and in group B was 8. 93%( 5 /56). The difference was not statistically significant( P = 0. 5567) despite of a growing trend in group A. The differences in the secondary efficacy endpoints between the two groups were not statistically significant( P > 0. 05). The pharmacodynamic parsameters such as the number of CD3+,CD4+and CD8+T cells at week 4 and 24 of group A were demonstrated a growing trend and reached the peak at week 4,but no significant differences( P> 0. 05) were found comparing with group B. Conclusion: The combination treatment of PEG-Tα1 and adefovir dipivoxil showed satisfactory safety,and promoted cellular immune responses. The efficacy would warrant further investigation in phase Ⅲ clinical trial in the near future.更多还原