文献标题：Tenofovir disoproxil fumarate for the treatment of chronic hepatitis B infection
文献出处：Health Technol Assess. 2010 May;14 Suppl 1:23-9.
文献类型：Review
期刊影响因子：6.910
PMID：20507800
本研究将Gilead生物技术公司及国家健康与临床优化研究所(NICE) 提交的证据作为单一技术评估过程的一部分，介绍了证据审查小组（ERG）对富马酸替诺福韦酯治疗慢性乙肝的临床疗效和成本效益的报告摘要。
所提交的临床证据包括两项替诺福韦和阿德福韦国际临床随机对照试验（RCTs）比较，以及使用直接和间接随机对照试验证据，通过贝叶斯法对替诺福韦与其他核苷(酸)类似物进行混合治疗比较（MTC）。虽然替诺福韦和阿德福韦的总不良事件没有显著统计学差异，但替诺福韦治疗组（HBeAg）阳性乙肝患者轻度恶心不良反应发生率较高。
“完全缓解”是一个复合终点，根据组织学反应和乙肝病毒DNA低于400拷贝/毫升来定义。对于HBeAg阳性和HBeAg阴性患者来说，替诺福韦治疗48周后，完全缓解比例明显比阿德福韦高。与阿德福韦相比，两组患者组织学反应没有显著统计学差异。由于其他亚群证据不足，MTC只对首次使用核苷(酸) 的e抗原阳性患者有效。应用替诺福韦达到乙肝病毒DNA检测不到概率要明显高于分析中其它疗法的0.05水平。
分析表明，就疗效而言，替诺福韦可能是最具潜力的核苷（酸）制剂。
医脉通推荐英文摘要：
Health Technol Assess. 2010 May;14 Suppl 1:23-9.
Tenofovir disoproxil fumarate for the treatment of chronic hepatitis B infection
Jones J, Colquitt J, Shepherd J, Harris P, Cooper K.
（Southampton Health Technology Assessments Centre, Wessex Institute, University of Southampton, Southampton, UK.）
This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of tenofovir disoproxil fumarate for the treatment of chronic hepatitis B, in accordance with the licensed indication, based upon the evidence submission from Gilead to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The submitted clinical evidence included two international randomised controlled trials (RCTs) comparing tenofovir with adefovir, and a mixed treatment comparison (MTC) using Bayesian methodology to compare tenofovir with other nucleos(t)ide analogues using direct and indirect RCT evidence. There were no statistically significant differences between tenofovir and adefovir in overall adverse events although, in hepatitis B 'e' antigen (HBeAg)-positive patients, there was a higher incidence of mild nausea in the tenofovir treatment group. The primary outcome, 'complete response', was a composite end point defined as histology response and hepatitis B virus DNA below 400 copies/ml. For both HBeAg-positive and HBeAg-negative patients, a significantly greater proportion had a complete response after 48 weeks with tenofovir than with adefovir. There was no statistically significant difference in histological response in either group of patients compared with adefovir. The MTC could only generate results for HBeAg positive nucleos(t)ide naive patients as there was insufficient evidence for other subgroups. The probability of achieving undetectable HBV DNA with tenofovir was found to be significantly higher than that for all other treatments considered in the analysis at the 0.05 level. The analysis demonstrated that there is a 98% probability that tenofovir is the most potent nucleos(t)ide in terms of this outcome. The manufacturer's submission concluded that tenofovir is a cost-effective option as first-line treatment. For HBeAg-positive patients, tenofovir followed by lamivudine has an incremental cost-effective ratio (ICER) of 9940 pounds per quality-adjusted life-year (QALY) gained, compared with lamivudine followed by tenofovir. A more appropriate treatment strategy of tenofovir followed by tenofovir plus lamivudine has an ICER of 13,619 pounds per QALY gained, compared with lamivudine followed by tenofovir. For HBeAg-negative patients, tenofovir followed by lamivudine has an ICER of 9811 pounds per QALY gained, compared with best supportive care. A more clinically appropriate treatment strategy of tenofovir followed by tenofovir plus lamivudine has an ICER of 13,854 pounds per QALY gained, compared with tenofovir followed by lamivudine. The ERG uncovered a number of errors in the submission and these ICERs approximately doubled when the analysis was corrected and reran. The guidance issued by NICE on 22 July 2009 states that tenofovir disoproxil, within its marketing authorization is recommended as an option for the treatment of people with chronic HBe-Ag-positive or HBe-Ag-negative hepatitis B in whom antiviral treatment is indicated.
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