Tran-Duy An, Boonen Annelies, Kievit Wietske, van Riel Piet L C M, van de Laar Mart A F J, Severens Johan L
Department of Clinical Epidemiology and Medical Technology Assessment (KEMTA), Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands,
Pharmacoeconomics. 2014 Oct;32(10):1015-28. doi: 10.1007/s40273-014-0184-4.
Management of rheumatoid arthritis (RA) is characterised by a sequence of disease-modifying antirheumatic drugs (DMARDs) and biological response modifiers (BRMs). In most of the Western countries, the drug sequences are determined based on disease activity and treatment history of the patients. A model for realistic patient outcomes should reflect the treatment pathways relevant for patients with specific characteristics.
This study aimed at developing a model that could simulate long-term patient outcomes and cost effectiveness of treatment strategies with and without inclusion of BRMs following a clinical guideline for treatment decisions.
Discrete event simulation taking into account patient characteristics and treatment history was used for model development. Treatment effect on disease activity, costs, health utilities and times to events were estimated using Dutch observational studies. Long-term progression of physical functioning was quantified using a linear mixed-effects model. Costs and health utilities were estimated using two-part models. The treatment strategy recommended by the Dutch Society for Rheumatology where both DMARDs and BRMs were available (Strategy 2) was compared with the treatment strategy without BRMs (Strategy 1). Ten thousand theoretical patients were tracked individually until death. In the probabilistic sensitivity analysis, Monte Carlo simulations were performed with 1,000 sets of parameters sampled from appropriate probability distributions.
The simulated changes over time in disease activity and physical functioning were plausible. The incremental cost per quality-adjusted life-year gained of Strategy 2 compared with Strategy 1 was
It is possible to model the outcomes of complex treatment strategies based on a clinical guideline for the management of RA. Following the Dutch guideline and using real-life data, inclusion of BRMs in the treatment strategy for RA appeared to be less favourable in our model than in most of the existing models that compared drug sequences independent of patient characteristics and used data from randomised controlled clinical trials. Despite complexity and demand for extensive data, our modelling approach can help to identify the knowledge gaps in clinical guidelines for RA management and priorities for future research.
类风湿关节炎（RA）的管理特点是使用一系列改善病情抗风湿药（DMARDs）和生物反应调节剂（BRMs）。在大多数西方国家，药物使用顺序是根据患者的疾病活动度和治疗史来确定的。一个反映现实患者预后的模型应体现与具有特定特征患者相关的治疗路径。
本研究旨在开发一个模型，该模型能够模拟遵循治疗决策临床指南使用和不使用BRMs的治疗策略的长期患者预后及成本效益。
模型开发采用考虑患者特征和治疗史的离散事件模拟。使用荷兰的观察性研究来估计治疗对疾病活动度、成本、健康效用和事件发生时间的影响。使用线性混合效应模型对身体功能的长期进展进行量化。使用两部分模型估计成本和健康效用。将荷兰风湿病学会推荐的同时有DMARDs和BRMs可用的治疗策略（策略2）与没有BRMs的治疗策略（策略1）进行比较。对一万名理论患者进行个体追踪直至死亡。在概率敏感性分析中，从适当的概率分布中抽取1000组参数进行蒙特卡洛模拟。
疾病活动度和身体功能随时间的模拟变化是合理的。与策略1相比，策略2每获得一个质量调整生命年的增量成本为124,011欧元。在支付意愿阈值高于119,167欧元时，策略2在成本效益方面优于策略1，但策略2具有成本效益的概率从未超过0.87。
基于RA管理的临床指南对复杂治疗策略的预后进行建模是可行的。遵循荷兰指南并使用实际数据，在我们的模型中，在RA治疗策略中纳入BRMs似乎不如大多数现有模型有利，那些现有模型比较了独立于患者特征的药物使用顺序并使用了随机对照临床试验的数据。尽管复杂且需要大量数据，但我们的建模方法有助于识别RA管理临床指南中的知识空白以及未来研究的重点。
