Veenstra David L, Sullivan Sean D, Clarke Lauren, Iloeje Uche H, Tafesse Eskinder, Di Bisceglie Adrian, Kowdley Kris V, Gish Robert G
Pharmaceutical Outcomes Research and Policy Program, Department of Pharmacy, University of Washington, Seattle, Washington 98195, USA.
Pharmacoeconomics. 2007;25(11):963-77. doi: 10.2165/00019053-200725110-00006.
To evaluate the cost effectiveness of treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) with entecavir compared with lamivudine with adefovir salvage, based primarily on the results of a recent 2-year, randomised, multicentre, clinical trial (n = 709). Previous economic analyses have been limited by the lack of comparative clinical data for entecavir and lamivudine beyond 1-year duration and for salvage therapy.
We conducted a cost-utility analysis using a Markov model from a US-payer perspective over a lifetime time horizon. The hypothetical cohort was 35-year-old patients with HBeAg-positive CHB. We evaluated 2 years of treatment with entecavir 0.5mg/day versus lamivudine 100mg/day, plus addition of adefovir 10mg/day for patients who developed virologic breakthrough due to resistance to either drug. In a scenario analysis, we considered adefovir plus lamivudine combination therapy for treatment-naive patients. Clinical and economic inputs ($US, year 2006 values) were derived from publicly available data, and probabilistic sensitivity analyses were conducted to evaluate uncertainty in the results.
The estimated 10-year cumulative incidence of cirrhosis for patients initiated on entecavir was 2.3% lower than for those on lamivudine (20.5% vs 22.8%). The discounted incremental cost per QALY gained was $US7600 in the base-case analysis, and the 95% central range from probabilistic sensitivity analysis was $US2500-$US19 100. Combination therapy for treatment-naive patients led to an increase in costs without improvement in patient outcomes compared with entecavir monotherapy.
Our analysis suggests entecavir improves health outcomes in a cost-effective manner compared with lamivudine with adefovir salvage or combination therapy, and highlights the importance of using evidence-based effectiveness estimates in economic studies of CHB therapies.
主要基于一项近期开展的为期2年的随机多中心临床试验(n = 709)结果,评估恩替卡韦与拉米夫定联合阿德福韦挽救治疗相比,用于治疗乙肝e抗原(HBeAg)阳性慢性乙型肝炎(CHB)的成本效益。既往的经济分析因缺乏恩替卡韦和拉米夫定超过1年疗程的比较临床数据以及挽救治疗的数据而受到限制。
我们从美国支付方的角度,使用马尔可夫模型在终身时间范围内进行了成本效用分析。假设队列是35岁的HBeAg阳性CHB患者。我们评估了每天服用0.5mg恩替卡韦与每天服用100mg拉米夫定治疗2年的情况,对于因对任一药物耐药而发生病毒学突破的患者加用每天10mg阿德福韦。在情景分析中,我们考虑了初治患者采用阿德福韦联合拉米夫定的联合治疗。临床和经济投入(2006年美元价值)来自公开可用数据,并进行了概率敏感性分析以评估结果的不确定性。
开始使用恩替卡韦治疗的患者估计10年肝硬化累积发生率比使用拉米夫定的患者低2.3%(20.5%对22.8%)。在基础病例分析中,每获得一个质量调整生命年(QALY)的贴现增量成本为7600美元,概率敏感性分析的95%中心范围为2500美元至19100美元。与恩替卡韦单药治疗相比,初治患者的联合治疗导致成本增加且患者结局无改善。
我们的分析表明,与拉米夫定联合阿德福韦挽救治疗或联合治疗相比,恩替卡韦以具有成本效益的方式改善了健康结局,并强调了在CHB治疗的经济研究中使用基于证据的有效性估计的重要性。