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肿瘤坏死因子-α抑制剂治疗类风湿关节炎的成本效用:贝叶斯方法在马尔可夫模型中证据综合的应用。

Cost utility of tumour necrosis factor-α inhibitors for rheumatoid arthritis: an application of Bayesian methods for evidence synthesis in a Markov model.

机构信息

Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.

出版信息

Pharmacoeconomics. 2012 Jul 1;30(7):575-93. doi: 10.2165/11594990-000000000-00000.

Abstract

BACKGROUND

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects approximately 1.5 million people in the US. Tumour necrosis factor (TNF)-α inhibitors have been shown to effectively treat and maintain remission in patients with moderately to severely active RA compared with conventional agents. The high acquisition cost of TNF-α inhibitors prohibits access, which mandates economic investigations into their affordability. The lack of head-to-head comparisons between these agents makes it difficult to determine which agent is the most cost effective.

OBJECTIVE

This study aimed to determine which TNF-α inhibitor was the most cost-effective agent for the treatment of moderately to severely active RA from the US healthcare payer's perspective.

METHODS

A Markov model was constructed to analyse the cost utility of five TNF-α inhibitors (in combination with methotrexate [+MTX]) versus MTX monotherapy using Bayesian methods for evidence synthesis. The model had a cycle length of 3 months and an overall time horizon of 5 years. Transition probabilities and utility scores were based on published studies. Total direct costs were adjusted to year 2009 $US using the medical component of the Consumer Price Index. All costs and QALYs were discounted at a rate of 3% per year. Patient response to the different strategies was determined by the American College of Rheumatology (ACR)50 criteria. One-way and probabilistic sensitivity analyses (PSAs) were performed to test the robustness of the base-case scenario. The base-case scenario was changed to ACR20 criteria (scenario 1) and ACR70 criteria (scenario 2) to determine the model's robustness. Cost-effectiveness acceptability curves and cost-effectiveness frontiers were used to estimate the cost-effectiveness probability of each treatment strategy. A willingness-to-pay (WTP) threshold was defined as three times the US GDP per capita ($US139,143 per additional QALY gained). Primary results were presented as incremental cost-effective ratios (ICERs).

RESULTS

Etanercept+MTX was the most cost-effective treatment strategy in the base-case scenario up to a WTP threshold of $US2 185,497 per QALY gained. At a WTP threshold of greater than $US2 185,497 per QALY gained, certolizumab+MTX was the most cost-effective treatment strategy. One-way analyses showed that the base-case scenario was sensitive to the probability of achieving ACR50 criteria for MTX and each TNF-α inhibitor, and changes in the utility score for patients who achieved the ACR50 criteria. With the exception of infliximab, all of the TNF-α inhibitors were sensitive to drug cost per cycle. In the scenario analyses, certolizumab+MTX was a dominant treatment strategy using ACR20 criteria, but etanercept+MTX was a dominant treatment strategy using ACR70 criteria.

CONCLUSIONS

Etanercept+MTX was a cost-effective treatment strategy in the base-case scenario; however, the model was sensitive to parameter uncertainties and ACR response criteria. Although Bayesian methods were used to determine transition probabilities, future studies will need to focus on head-to-head comparisons of multiple TNF-α inhibitors to provide valid comparisons.

摘要

背景

类风湿关节炎(RA)是一种慢性自身免疫性疾病,影响美国约 150 万人。与传统药物相比,肿瘤坏死因子(TNF)-α抑制剂已被证明可有效治疗和维持中度至重度活动期 RA 患者的缓解。由于 TNF-α 抑制剂的高获得成本限制了其使用,因此需要从美国医疗支付方的角度对其经济可负担性进行经济研究。由于这些药物之间缺乏头对头比较,因此很难确定哪种药物最具成本效益。

目的

本研究旨在从美国医疗支付方的角度确定治疗中度至重度活动期 RA 时哪种 TNF-α 抑制剂是最具成本效益的药物。

方法

使用贝叶斯方法进行证据综合,构建了一个 Markov 模型,以分析五种 TNF-α 抑制剂(联合甲氨蝶呤[+MTX])与 MTX 单药治疗的成本效用,模型的周期长度为 3 个月,总时间范围为 5 年。转移概率和效用评分基于已发表的研究。使用消费者价格指数的医疗组成部分将总直接成本调整为 2009 年的美元。所有成本和 QALYs 均按每年 3%的贴现率贴现。不同策略的患者反应由美国风湿病学会(ACR)50 标准确定。进行了单因素和概率敏感性分析(PSA)以测试基本情况假设的稳健性。将基本情况假设更改为 ACR20 标准(方案 1)和 ACR70 标准(方案 2),以确定模型的稳健性。成本效益接受曲线和成本效益前沿用于估计每种治疗策略的成本效益概率。定义了一个意愿支付(WTP)阈值,即美国人均国内生产总值(GDP)的三倍(每增加一个 QALY 获益$US139,143)。主要结果以增量成本效益比(ICER)表示。

结果

在 WTP 阈值为每增加一个 QALY 获益$US2 185,497 以内,依那西普+MTX 是基本情况假设中最具成本效益的治疗策略。在 WTP 阈值大于每增加一个 QALY 获益$US2 185,497 时,培塞利珠单抗+MTX 是最具成本效益的治疗策略。单因素分析表明,基本情况假设对 MTX 和每种 TNF-α 抑制剂达到 ACR50 标准的概率以及达到 ACR50 标准的患者效用评分的变化敏感。除英夫利昔单抗外,所有 TNF-α 抑制剂对每周期药物成本均敏感。在方案分析中,培塞利珠单抗+MTX 是使用 ACR20 标准的主导治疗策略,但依那西普+MTX 是使用 ACR70 标准的主导治疗策略。

结论

在基本情况假设中,依那西普+MTX 是一种具有成本效益的治疗策略;然而,该模型对参数不确定性和 ACR 反应标准敏感。尽管使用了贝叶斯方法来确定转移概率,但未来的研究仍需要侧重于多种 TNF-α 抑制剂的头对头比较,以提供有效的比较。

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