替比夫定治疗慢性乙肝的疗效优于拉米夫定

来源：新特药房药讯作者：百济动态浏览：发布时间：2008/1/4 13:42:00

《新英格兰医学杂志》2007年12月20日报道称，一项双盲、三期试验结果表明，尽管拉米夫定（lamivudine）是目前应用最广泛的抗乙肝制剂，但是替比夫定（telbivudine）抵抗乙型肝炎病毒（HBV）感染的效果要优于拉米夫定。

香港玛丽医院的医学博士黎青龙教授和国际研究组的同事在报告中指出：“将HBV复制降低到最低水平正逐步成为治疗慢性乙肝的主要目标……Telbivudine（β-L-2′-脱氧胸苷）是一种口服的左旋核苷类似物，是一种高效、特异性的HBV抑制剂。一项特别针对生育年龄的人群进行的临床前毒理试验结果显示，telbivudine不会引起基因突变或致癌，也没有明显的胚胎或胎儿毒性效应。”

在这项国际试验中，1370名慢性HBV感染患者随机接受每日一次600mg的telbivudine或每日一次100 mg的lamivudine。这是一项telbivudine和lamivudine的非劣性试验，主要疗效指标为“治疗应答”，即血清HBV DNA < 5 log10 copies/mL、HBeAg转阴或ALT水平转为正常。次要疗效指标为“组织学应答”，包括HBV DNA水平和HBeAg应答。

在第52周，与接受lamivudine治疗的患者相比，服用telbivudine的HBeAg阳性患者发生治疗应答（75.3% vs67.0%；P=.005）或组织学应答（64.7% vs 56.3%; P =0.01）的比例更大。在HBeAg阴性患者中，telbivudine的治疗应答和组织学应答也丝毫不逊色于lamivudine。

在HBeAg阴性和HBeAg阳性研究组中，telbivudine的几项疗效指标都优于lamivudine，包括HBV DNA较基线的平均下降值、HBV DNA下降到PCR检测不到水平的患者所占比例、耐药性的发展等。

研究人员写到：“在HBeAg阳性慢性乙肝患者中，使用telbivudine治疗的患者，第1年的治疗应答和组织学应答概率明显高于使用lamivudine治疗的患者。在HBeAg阴性组和HBeAg阳性组中，telbivudine比lamivudine更能有效抑制HBV DNA复制。”

服用telbivudine的患者中更容易出现肌酸激酶水平升高，而在接受lamivudine治疗的患者中，关于谷丙转氨酶和天门冬氨酸转氨酶升高的报道则更加频繁。

研究人员最后总结说：“目前乙型肝炎已经有多种治疗方法可供选择，这就促使医务人员更加注重控制HBV复制的长期疗效，最终达到提高临床疗效的目的。此次的研究结果证实了telbivudine能够有效治疗慢性乙肝。”

原文：

Telbivudine May Be More Effective Than Lamivudine for Chronic Hepatitis B

December 19, 2007 — Although lamivudine is the most widely prescribed anti–hepatitis B agent, telbivudine may be more effective than lamivudine for chronic hepatitis B virus (HBV) infection, according to the results of a double-blind, phase 3 trial reported in the December 20 issue of the New England Journal of Medicine.

"Reducing hepatitis B virus (HBV) replication to minimal levels is emerging as a key therapeutic goal for chronic hepatitis B," write Ching-Lung Lai, MD, from the University Department of Medicine, Queen Mary Hospital in Hong Kong, and colleagues from the Globe Study Group. "Telbivudine (β-L-2′-deoxythymidine) is an orally bioavailable L-nucleoside with potent and specific anti-HBV activity. In preclinical toxicologic testing, telbivudine had no mutagenic or carcinogenic effects and no appreciable embryonic or fetal toxic effects —findings that are particularly relevant for men and women in their reproductive years."

In the Globe trial, 1370 patients with chronic HBV infection were randomized to receive 600 mg of telbivudine or 100 mg of lamivudine once daily. This was a noninferiority trial of telbivudine to lamivudine for therapeutic response, defined as a reduction in serum HBV DNA levels to less than 5 log10 copies/mL, as well as loss of hepatitis B e antigen (HBeAg) or normalization of alanine aminotransferase levels. Secondary efficacy endpoints were histologic response, changes in serum HBV DNA levels, and HBeAg responses.

Compared with patients receiving lamivudine, a greater proportion of patients with positive HBeAg who were receiving telbivudine had a therapeutic response (75.3% vs 67.0%; P = .005) or a histologic response (64.7% vs 56.3%; P = .01) at week 52. In patients with negative HBeAg, telbivudine was also not inferior to lamivudine for therapeutic or histologic response.

In both the HBeAg-negative and HBeAg-positive groups, telbivudine was superior to lamivudine for several outcome measures, including mean reduction from baseline in the number of copies of HBV DNA, the proportion of patients with a decrease in HBV DNA to levels undetectable by polymerase-chain-reaction assay, and development of drug resistance.

"Among patients with HBeAg-positive chronic hepatitis B, the rates of therapeutic and histologic response at 1 year were significantly higher in patients treated with telbivudine than in patients treated with lamivudine," the study authors write. "In both the HBeAg-negative and the HBeAg-positive groups, telbivudine demonstrated greater HBV DNA suppression with less resistance than did lamivudine."

In laboratory abnormalities, elevated creatine kinase levels were more frequently reported in patients who received telbivudine, but elevated alanine aminotransferase and aspartate aminotransferase levels were more frequently reported in patients who received lamivudine. "The multiple therapeutic choices now available for hepatitis B will enhance the ability of clinicians to maintain long-term control of HBV replication, ultimately improving clinical outcomes for more patients," the study authors conclude. "These results support telbivudine as an effective therapy for patients with chronic hepatitis B."

分享到：