Department of Pneumology, Hospital Universitari Vall dHebron, CIBERES, Barcelona, Catalonia, Spain.
Appl Health Econ Health Policy. 2012 May 1;10(3):175-88. doi: 10.2165/11630780-000000000-00000.
Pulmonary arterial hypertension (PAH) is considered an orphan disease. Prostacyclins are the keystone for PAH treatment. Choosing between the three available prostacyclin therapies could be complicated because there are no comparison studies, so the final decision must be driven by factors such as efficacy, administration route, safety profile and economic aspects.
This study provides a cost-effectiveness and cost-utility comparison of initiating prostacyclin therapy with three different treatment alternatives (inhaled iloprost [ILO], intravenous epoprostenol [EPO] and subcutaneous treprostinil [TRE]) for patients with PAH. The goal of this work is to help physicians with their therapeutic decision-making.
A Markov model was built to simulate a patient cohort with class III PAH according to the classification of the New York Heart Association (NYHA). Four health states corresponding with the NYHA classes plus death were allowed for patients in the model. Changing the treatment was possible when patients worsened from functional class III to IV. The time horizon was 3 years, allowing patients to transition between health states on a 12-week cycle basis. The study perspective was that of the National Health System (NHS) [only direct medical costs were included]. Unitary costs were obtained from the Drug Catalogue and e-Salud Database in 2009 and are given in euros (€). Data on health resources and treatment pathways were informed by a four-member expert panel. Efficacy was obtained from pivotal clinical trials of ILO, EPO and TRE, the latter used in Spain as a foreign medication. Utilities for each health state were obtained from the literature. The final efficacy measure was life-years gained (LYG), and utilities were used to obtain quality-adjusted life-years (QALYs). Costs and effects were discounted at a 3% rate. To check for the robustness of the results, sensitivity analyses were performed.
At the end of the 3 years, in the base case of the deterministic analysis, initiating prostacyclin therapy with iloprost was the less costly strategy (€132,840), followed by treprostinil (€359,869) and epoprostenol (€429,775). Epoprostenol has shown the best efficacy results with 2.73 LYG and 1.78 QALY, followed by iloprost (2.69 LYG and 1.74 QALY) and treprostinil (2.69 LYG and 1.73 QALY). Incremental cost-effectiveness ratios (ICER) and cost-utility ratios (ICUR) of epoprostenol versus iloprost and treprostinil were much above the €30,000 per LYG or QALY threshold commonly used in Spain. Iloprost was dominant compared with treprostinil. In the probabilistic analysis, epoprostenol, when compared with iloprost, was a dominant strategy in 15% of the simulations, but it was not a cost-effective option in 83% of the cases. When compared with treprostinil, epoprostenol was dominant in 43% of the simulations. Iloprost was dominant compared with treprostinil in 45% of the cases and it was a cost-effective alternative in 39% of the simulations.
Initiating prostacyclin treatment with iloprost in patients with PAH, functional class III of the NYHA, is the less costly alternative for the NHS in Spain, with a good efficacy profile when compared with the other alternatives.
肺动脉高压（PAH）被认为是一种孤儿病。前列腺素是 PAH 治疗的基石。由于没有比较研究，因此在选择三种可用的前列腺素治疗方法时可能会很复杂，因此最终决定必须取决于疗效、给药途径、安全性和经济方面等因素。
本研究比较了三种不同治疗选择（吸入伊洛前列素[ILO]、静脉内依前列醇[EPO]和皮下曲前列尼尔[TRE]）开始前列腺素治疗 PAH 患者的成本效益和成本效用。本研究的目的是帮助医生做出治疗决策。
建立了一个马尔可夫模型，根据纽约心脏协会（NYHA）的分类模拟了一组 III 类 PAH 患者。模型允许患者在四个健康状态之间转换，对应 NYHA 类别加上死亡。当患者从功能 III 类恶化到 IV 类时，可以改变治疗方法。时间范围为 3 年，允许患者在 12 周的周期内从一个健康状态过渡到另一个健康状态。研究视角是国家卫生系统（NHS）[仅包括直接医疗费用]。单位成本从 2009 年的药物目录和电子健康数据库中获得，以欧元（€）表示。健康资源和治疗途径的数据由一个由四名专家组成的小组提供。从 ILO、EPO 和 TRE 的关键临床试验中获得疗效数据，后者在西班牙作为一种外国药物使用。从文献中获得每个健康状态的效用。最终的疗效衡量标准是生命年获益（LYG），效用用于获得质量调整生命年（QALY）。成本和效果以 3%的利率贴现。为了检查结果的稳健性，进行了敏感性分析。
在 3 年的时间内，在确定性分析的基础情况下，使用伊洛前列素开始前列腺素治疗的策略成本最低（€132840），其次是曲前列尼尔（€359869）和依前列醇（€429775）。依前列醇的疗效最好，有 2.73 LYG 和 1.78 QALY，其次是伊洛前列素（2.69 LYG 和 1.74 QALY）和曲前列尼尔（2.69 LYG 和 1.73 QALY）。依前列醇与伊洛前列素和曲前列尼尔相比，增量成本效益比（ICER）和成本效用比（ICUR）远高于西班牙通常使用的 30000 欧元/LYG 或 QALY 阈值。伊洛前列素与曲前列尼尔相比具有优势。在概率分析中，与伊洛前列素相比，依前列醇在 15%的模拟中是一种占主导地位的策略，但在 83%的情况下不是一种具有成本效益的选择。与曲前列尼尔相比，依前列醇占主导地位的情况占 43%。与曲前列尼尔相比，依前列醇在 45%的模拟中占主导地位，在 39%的模拟中是一种具有成本效益的选择。
在西班牙 NHS 中，对于 NYHA 功能 III 类的 PAH 患者，使用伊洛前列素开始前列腺素治疗是成本较低的选择，与其他选择相比，具有良好的疗效。
