1 Comprehensive Health Insights, Humana, Louisville, Kentucky.
2 Humana, Louisville, Kentucky.
J Manag Care Spec Pharm. 2016 Jul;22(7):863-71. doi: 10.18553/jmcp.2016.22.7.863.
Chronic hepatitis C virus (HCV) is the primary cause of liver failure leading to transplantation, and medication adherence is essential to the therapeutic efficacy of HCV treatments. While there is evidence linking poor adherence with increased utilization and cost, published literature lacks examination of the association between medication adherence and risk of liver transplant. In addition, the impact of HCV treatment on total costs of liver transplantation is not well documented.
To compare (a) the relative risk of liver transplant by adherence in patients treated for HCV and (b) the total health care costs in treated and untreated patients who require liver transplant.
This observational, historical cohort study was conducted using administrative data from the Humana Research Database. To be included, patients were required to have a documented HCV diagnosis or treatment between January 1, 2008, and June 30, 2013. Patients were excluded if they had a hepatitis B diagnosis, were not fully insured by a commercial or Medicare Advantage Prescription Drug plan, or were outside the age range of 19-89 years. No minimum pre- or post-index enrollment period was required, and patients were followed for their entire post-index enrollment through December 31, 2013. The study population was divided into treated and untreated groups and then subdivided by presence or absence of a liver transplant. Date of liver transplant was defined as the index date for untreated liver transplant patients; otherwise, the index date was defined as either the date of first observed HCV treatment or diagnosis date (if no treatment or liver transplant). Cox proportional hazards models were used to estimate the relative risk of liver transplant by level of treatment adherence (> 80%, 50%-79%, and < 50%) based on proportion of days covered. General linearized models with log link and gamma distribution were used to compare median total health care costs from index date until end of study period (or death/disenrollment, whichever came first) between treated and untreated liver transplant patients. All costs were converted to 2013 U.S. dollars and reported as total costs per patient and per patient per month (PPPM) to account for varying follow-up periods.
Of the 53,423 patients identified with HCV, 10,377 met exclusion criteria, leaving 43,046 patients (primarily Caucasian, males, mean age of 58 years) in the initial cohort. Only 6.29% (n = 2,708) of the total HCV cohort received HCV treatment, and less than 1% (n = 366, 0.8%) received a liver transplant. Although there were no significant differences in the risk of liver transplant by adherence level, there was an upwards trend in the rate of liver transplant as adherence worsened (> 80%: 1.25%; 50%-79%: 1.30%; and < 50%: 1.99%), and the average days to liver transplant was longer with higher adherence (> 80%: 683; 50%-79%: 623; < 50%: 454). Only 48 (13.11%) patients who received a liver transplant were treated for HCV. Adjusted median total and PPPM health care costs measured from index date until end of the study period were significantly higher for patients who received HCV treatment compared with those who did not (total=$231,139 vs. $86,167, adjusted P < 0.001; PPPM=$20,583 vs. $5,778, adjusted P = 0.008), driven by HCV-related medical costs and total pharmacy costs.
Adherence with HCV regimens did not affect risk of liver transplant, underscoring the need for further evidence linking treatment adherence to future liver transplant risk. HCV-treated patients who required liver transplant incurred significantly higher health care costs than those without HCV treatment before liver transplant. Introduction of newer all-oral direct-acting antiviral regimens, with higher acquisition costs, will require further research to more accurately assess medication adherence and its relationship with transplantation, as well as with total health care costs.
No outside funding supported this research. Ems, Worley, Racsa, Gregory, Anderson, and Holt are employees of Humana. Brill has participated in a physician advisory board at Humana. The authors have no other financial disclosures to report. Study concept and design were contributed by Ems, Racsa, Worley, and Anderson, along with Gregory, Brill, and Holt. Racsa took the lead in data collection, along with Ems and Worley. All authors participated in data interpretation. Anderson, along with the other authors, wrote the manuscript, which was revised by Brill and Holt, with assistance from the other authors.
慢性丙型肝炎病毒（HCV）是导致肝衰竭进而需要进行肝移植的主要原因，而坚持用药对于 HCV 治疗的疗效至关重要。虽然有证据表明，坚持用药与利用率和成本增加有关，但已发表的文献缺乏对用药依从性与肝移植风险之间关联的研究。此外，HCV 治疗对肝移植总成本的影响也没有得到很好的记录。
比较（a）接受 HCV 治疗的患者中，药物依从性与肝移植风险的相对风险，以及（b）需要肝移植的治疗和未治疗患者的总医疗保健成本。
这项观察性、历史性队列研究使用了来自 Humana Research Database 的管理数据。纳入标准为：患者在 2008 年 1 月 1 日至 2013 年 6 月 30 日期间有 HCV 诊断或治疗记录。排除标准为：有乙型肝炎诊断记录、未完全通过商业或 Medicare Advantage 处方药计划投保，或年龄不在 19-89 岁之间。对入组前和入组后的时间没有最低要求，从患者的索引日期开始，一直随访至 2013 年 12 月 31 日。研究人群分为治疗组和未治疗组，然后根据是否进行了肝移植进一步细分。未治疗肝移植患者的肝移植日期定义为索引日期；否则，索引日期定义为首次观察到 HCV 治疗或诊断日期（如果没有治疗或肝移植）。基于比例天数覆盖情况，使用 Cox 比例风险模型估计了不同用药依从性水平（>80%、50%-79%和<50%）的肝移植相对风险。使用具有对数链接和伽马分布的广义线性化模型，比较了治疗和未治疗肝移植患者从索引日期到研究结束日期（或死亡/退出，以先发生者为准）的中位总医疗保健成本。所有成本均转换为 2013 年美元，并报告为每位患者和每位患者每月（PPPM）的总费用，以考虑到不同的随访时间。
在 53423 名 HCV 患者中，有 10377 名患者符合排除标准，因此初始队列中剩余 43046 名患者（主要为白种人，男性，平均年龄 58 岁）。仅有 6.29%（n=2708）的 HCV 患者接受了 HCV 治疗，不到 1%（n=366，0.8%）的患者接受了肝移植。尽管依从性水平与肝移植风险之间没有显著差异，但随着依从性的恶化，肝移植的发生率呈上升趋势（>80%：1.25%；50%-79%：1.30%；<50%：1.99%），且随着依从性的提高，到达肝移植的平均时间也延长（>80%：683；50%-79%：623；<50%：454）。只有 48 名接受肝移植的患者接受了 HCV 治疗。从索引日期到研究结束日期，接受 HCV 治疗的患者的中位总医疗保健成本和每位患者每月成本（PPPM）均显著高于未接受治疗的患者（总费用：$231139 比 $86167，调整后 P<0.001；PPPM：$20583 比 $5778，调整后 P=0.008），这主要是由于 HCV 相关医疗费用和总药房费用所致。
HCV 治疗方案的依从性与肝移植风险无关，这突显出需要进一步证明治疗依从性与未来肝移植风险之间的关系。需要进行肝移植的 HCV 治疗患者的医疗保健成本显著高于未接受 HCV 治疗的患者，且在肝移植之前就已经发生。新型全口服直接作用抗病毒药物方案的引入，具有更高的获取成本，需要进一步研究来更准确地评估药物依从性及其与移植的关系，以及与总体医疗保健成本的关系。
本研究无外部资金支持。Ems、Worley、Racsa、Gregory、Anderson 和 Holt 是 Humana 的员工。Brill 曾参与 Humana 的医师顾问委员会。作者没有其他财务披露。Ems、Racsa、Worley 和 Anderson 与 Gregory、Brill 和 Holt 一起提出了研究概念和设计，并与 Racsa、Ems 和 Worley 一起进行了数据收集。所有作者均参与了数据解释。Anderson 与其他作者一起撰写了手稿，Brill 和 Holt 对其进行了修订，并得到了其他作者的协助。
