Incerti Devin, Hernandez Ervant J Maksabedian, Tkacz Joseph, Jansen Jeroen P, Collier David, Gharaibeh Mahdi, Moore-Schiltz Laura, Stolshek Bradley S
Precision Health Economics, Oakland, California.
Amgen, Thousand Oaks, California.
J Manag Care Spec Pharm. 2020 Oct;26(10):1236-1242. doi: 10.18553/jmcp.2020.26.10.1236.
Patients with moderate to severe rheumatoid arthritis (RA) occasionally increase their doses of tumor necrosis factor (TNF) inhibitors, especially the monoclonal antibody origin drugs such as adalimumab and infliximab, after inadequate response to the initial dose. Previous studies have evaluated the cost-effectiveness of various sequences of treatment for RA in the United States but have not considered the effect of dose escalation.
To assess the cost-effectiveness of etanercept and adalimumab by incorporating the effect of dose escalation in moderate to severe RA patients.
We adapted the open-source Innovation and Value Initiative - Rheumatoid Arthritis model, version 1.0 to separately simulate the magnitude and time to dose escalation among RA patients taking adalimumab plus methotrexate or etanercept plus methotrexate from a societal perspective and lifetime horizon. An important assumption in the model was that dose escalation would increase treatment costs through its effect on the number of doses but would have no effect on effectiveness. We estimated the dose escalation parameters using the IBM MarketScan Commercial and Medicare Supplemental Databases. We fit competing parametric survival models to model time to dose escalation and used model diagnostics to compare the fit of the competing models. We measured the magnitude of dose escalation as the percentage increase in the number of doses conditional on dose escalation. Finally, we used the parameterized model to simulate treatment sequences beginning with a TNF inhibitor (adalimumab, etanercept) followed by nonbiologic treatment.
In baseline models without dose escalation, the incremental cost per quality-adjusted life-year of the etanercept treatment sequence relative to the adalimumab treatment sequence was $85,593. Incorporating dose escalation increased treatment costs for each sequence, but costs increased more with adalimumab, lowering the incremental cost-effectiveness ratio to $9,001. At willingness-to-pay levels of $100,000, the etanercept sequence was more cost-effective compared with the adalimumab sequence, with probability 0.55 and 0.85 in models with and without dose escalation, respectively.
Dose escalation has important effects on cost-effectiveness and should be considered when comparing biologic medications for the treatment of RA.
Funding for this study was contributed by Amgen. When this work was conducted, Incerti and Jansen were employees of Precision Health Economics, which received financial support from Amgen. Maksabedian Hernandez, Collier, Gharaibeh, and Stolshek were employees and stockholders of Amgen, and Tkacz and Moore-Schiltz were employees of IBM Watson Health, which received financial support from Amgen. Some of the results of this work were previously presented as a poster at the 2019 AMCP Managed Care & Specialty Pharmacy Annual Meeting, March 25-28, 2019, in San Diego, CA.
中重度类风湿关节炎（RA）患者在初始剂量治疗反应不足后，偶尔会增加肿瘤坏死因子（TNF）抑制剂的剂量，尤其是阿达木单抗和英夫利昔单抗等单克隆抗体类药物。此前的研究评估了美国RA各种治疗方案的成本效益，但未考虑剂量增加的影响。
通过纳入中重度RA患者剂量增加的影响，评估依那西普和阿达木单抗的成本效益。
我们采用开源的创新与价值倡议 - 类风湿关节炎模型1.0版，从社会角度和终身视角分别模拟接受阿达木单抗加甲氨蝶呤或依那西普加甲氨蝶呤治疗的RA患者剂量增加的幅度和时间。该模型的一个重要假设是，剂量增加会因其对剂量数量的影响而增加治疗成本，但对疗效无影响。我们使用IBM MarketScan商业和医疗保险补充数据库估计剂量增加参数。我们拟合竞争参数生存模型以模拟剂量增加的时间，并使用模型诊断比较竞争模型的拟合情况。我们将剂量增加的幅度衡量为剂量增加条件下剂量数量的百分比增长。最后，我们使用参数化模型模拟以TNF抑制剂（阿达木单抗、依那西普）开始随后进行非生物治疗的治疗方案。
在无剂量增加的基线模型中，依那西普治疗方案相对于阿达木单抗治疗方案每质量调整生命年的增量成本为85,593美元。纳入剂量增加会使每个方案的治疗成本增加，但阿达木单抗方案成本增加更多，将增量成本效益比降至9,001美元。在支付意愿水平为100,000美元时，依那西普方案与阿达木单抗方案相比更具成本效益，在有和无剂量增加的模型中，概率分别为0.55和0.85。
剂量增加对成本效益有重要影响，在比较治疗RA的生物药物时应予以考虑。
本研究的资金由安进公司提供。开展这项工作时，因塞尔蒂和扬森是Precision Health Economics公司的员工，该公司接受了安进公司的财政支持。马克萨贝迪安·埃尔南德斯、科利尔、加拉伊贝和斯托尔舍克是安进公司的员工和股东，而特卡茨和摩尔 - 席尔茨是IBM Watson Health公司的员工，该公司接受了安进公司的财政支持。这项工作的一些结果曾在2019年3月25 - 28日于加利福尼亚州圣地亚哥举行的2019年美国医学成本管理协会（AMCP）管理式医疗与专科药房年会上以海报形式展示。
