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阿德福韦酯与聚乙二醇化干扰素α-2a治疗慢性乙型肝炎的系统评价与经济学评估

A systematic review and economic evaluation of adefovir dipivoxil and pegylated interferon-alpha-2a for the treatment of chronic hepatitis B.

作者信息

Takeda A, Jones J, Shepherd J, Davidson P, Price A

机构信息

Southampton Health Technology Assessments Centre, University of Southampton, Boldrewood, Southampton, UK.

出版信息

J Viral Hepat. 2007 Feb;14(2):75-88. doi: 10.1111/j.1365-2893.2006.00808.x.

Abstract

Standard treatments for chronic hepatitis B (CHB) include interferon-alpha (IFN-alpha) and lamivudine (LAM), but these are associated with adverse effects and viral resistance, respectively. The aim of this systematic review and economic evaluation was to assess the clinical effectiveness and cost-effectiveness of two alternative drugs for the treatment of adults with CHB: adefovir dipivoxil (ADV) and pegylated IFN-alpha-2a. We searched electronic databases, including Cochrane Systematic Reviews and Medline, for literature that met criteria defined in a research protocol. Retrieved articles were independently assessed for inclusion by two reviewers. We developed a Markov state transition model to estimate the cost-effectiveness (cost-utility) of pegylated IFN-alpha-2a and of ADV compared with nonpegylated IFN-alpha-2a, LAM and best supportive care. Seven randomized controlled trials and two systematic reviews met the inclusion criteria for our review of clinical effectiveness. ADV was significantly more effective than placebo or ongoing LAM in reducing levels of hepatitis B virus (HBV) DNA. Rates of hepatitis B e antigen (HBeAg) seroconversion were higher among patients receiving ADV than either placebo or ongoing LAM. Patients treated with pegylated IFN-alpha-2a, either as monotherapy or in combination with LAM, showed significantly reduced HBV DNA levels compared with patients treated with LAM monotherapy. HBeAg seroconversion rates at follow-up were significantly higher for pegylated IFN-alpha-2a patients than for those receiving LAM monotherapy. Results of our cost-effectiveness analysis demonstrate that incremental costs per quality adjusted life year (QALY) for a range of comparisons were between 5,994 and 16,569 British Pound, and within the range considered by NHS decision-makers to represent good value for money.

摘要

慢性乙型肝炎(CHB)的标准治疗方法包括α干扰素(IFN-α)和拉米夫定(LAM),但这些治疗方法分别存在不良反应和病毒耐药性问题。本系统评价和经济学评估的目的是评估两种用于治疗成人CHB的替代药物的临床有效性和成本效益:阿德福韦酯(ADV)和聚乙二醇化α-2a干扰素。我们检索了电子数据库,包括Cochrane系统评价和Medline,以查找符合研究方案中定义标准的文献。两名评审员独立评估检索到的文章是否纳入。我们建立了一个马尔可夫状态转换模型,以估计聚乙二醇化α-2a干扰素和ADV与非聚乙二醇化α-2a干扰素、LAM及最佳支持治疗相比的成本效益(成本效用)。七项随机对照试验和两项系统评价符合我们临床有效性评价的纳入标准。在降低乙肝病毒(HBV)DNA水平方面,ADV比安慰剂或继续使用LAM显著更有效。接受ADV治疗的患者中乙肝e抗原(HBeAg)血清学转换率高于接受安慰剂或继续使用LAM的患者。与接受LAM单药治疗的患者相比,接受聚乙二醇化α-2a干扰素单药治疗或与LAM联合治疗的患者HBV DNA水平显著降低。随访时,聚乙二醇化α-2a干扰素治疗患者的HBeAg血清学转换率显著高于接受LAM单药治疗的患者。我们的成本效益分析结果表明,一系列比较中的每质量调整生命年(QALY)增量成本在5994至16569英镑之间,且在英国国家医疗服务体系(NHS)决策者认为代表性价比良好的范围内。

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