Leonard D. Schaeffer Center for Health Policy & Economics, Los Angeles, California.
Inflammatory Bowel Disease Center, Division of Gastrointestinal and Liver Disease, USC/Keck School of Medicine, Los Angeles, California.
Pharmacotherapy. 2019 Feb;39(2):118-128. doi: 10.1002/phar.2208. Epub 2019 Jan 20.
Ustekinumab was recently approved by the United States U.S. Food and Drug Administration for the treatment of Crohn's disease. In this analysis, we aimed to compare the cost-effectiveness of ustekinumab, infliximab, or adalimumab for the treatment of moderate-severe Crohn's disease in patients who failed conventional therapy (i.e., corticosteroids and immunomodulators) but were naïve to tumor necrosis factor antagonists (i.e., biologic drugs).
Cost-effectiveness analysis using a hybrid model structure (decision tree and Markov model).
A decision tree simulated biologic induction, and a Markov model simulated biologic and conventional therapy maintenance. Cycle length was 2 weeks with a discounted 5-year time horizon and a limited U.S. societal perspective in the base case; results from a payer perspective are also reported. Transition probabilities, direct costs, indirect costs, and utilities were obtained from the literature. To measure relative treatment value (i.e., order of treatment cost-effectiveness), net monetary benefits were reported for a $150,000 willingness-to-pay threshold per quality-adjusted life-year in the base case. Infliximab dominated both adalimumab and ustekinumab, with a net monetary benefit (NMB) of $9943 and $29,798, respectively, in the base case. Adalimumab dominated ustekinumab, with an NMB of $19,855. All biologics yielded similar quality-adjusted life-years (~3.5), whereas costs varied substantially ($50,510, $54,985, and $72,921 for infliximab, adalimumab, and ustekinumab, respectively). The payer perspective, alternate time horizons, and scenario analyses consistently showed infliximab dominance. One-way, threshold, and probabilistic sensitivity analyses confirmed the robustness of these results with respect to all parameters. Although biosimilars were not explicitly modeled as comparators, one-way sensitivity analysis showed that drug acquisition costs could alter relative treatment value but would have to be varied by at least 50%.
For moderate-severe Crohn's disease, infliximab yields significantly more NMBs compared with both adalimumab and ustekinumab. Additional clinical (e.g., empiric dosing, biologic cycling) and quality-of-life (e.g., lost productivity, disutility of home injections) research is needed to allow for model frameworks and parameters that more accurately reflect the nuances of Crohn's disease treatment.
乌司奴单抗最近被美国食品和药物管理局批准用于治疗克罗恩病。在这项分析中,我们旨在比较乌司奴单抗、英夫利昔单抗或阿达木单抗治疗对常规治疗(即皮质类固醇和免疫调节剂)失败但对肿瘤坏死因子拮抗剂(即生物药物)无反应的中重度克罗恩病患者的成本效益。
使用混合模型结构(决策树和马尔可夫模型)进行成本效益分析。
决策树模拟生物诱导,马尔可夫模型模拟生物和常规治疗维持。在基础案例中,周期长度为 2 周,贴现 5 年时间范围和有限的美国社会视角;还报告了来自支付者的结果。转移概率、直接成本、间接成本和效用均来自文献。为了衡量相对治疗价值(即治疗成本效益的顺序),在基础案例中,每质量调整生命年 150,000 美元的意愿支付阈值报告了净货币收益。英夫利昔单抗优于阿达木单抗和乌司奴单抗,基础案例中的净货币收益(NMB)分别为 9943 美元和 29798 美元。阿达木单抗优于乌司奴单抗,NMB 为 19855 美元。所有生物制剂的质量调整生命年相似(~3.5),而成本差异很大(英夫利昔单抗、阿达木单抗和乌司奴单抗分别为 50510 美元、54985 美元和 72921 美元)。支付者视角、替代时间范围和情景分析一致表明英夫利昔单抗占主导地位。单向、阈值和概率敏感性分析证实了这些结果对所有参数的稳健性。尽管生物类似物没有明确建模为比较剂,但单向敏感性分析表明,药物收购成本可能会改变相对治疗价值,但必须至少变化 50%。
对于中重度克罗恩病,与阿达木单抗和乌司奴单抗相比,英夫利昔单抗产生的 NMB 显著更高。需要进行更多的临床(例如经验性给药、生物循环)和生活质量(例如失去生产力、家庭注射的不适)研究,以允许更准确地反映克罗恩病治疗细微差别的模型框架和参数。