Statesia, Le Mans, France.
MSD FRANCE, Paris, France.
PLoS One. 2018 Mar 15;13(3):e0194329. doi: 10.1371/journal.pone.0194329. eCollection 2018.
To assess the cost-effectiveness of the elbasvir/grazoprevir (EBR/GZR) regimen in patients with genotype 1 chronic hepatitis C virus (HCV) infection with severe and end-stage renal disease compared to no treatment.
This study uses a health economic model to estimate the cost-effectiveness of treating previously untreated and treatment experienced chronic hepatitis C patients who have severe and end stage renal disease with the elbasvir-grazoprevir regimen versus no treatment in the French context. The lifetime homogeneous markovian model comprises of forty combined health states including hepatitis C virus and chronic kidney disease. The model parameters were from a multicentre randomized controlled trial, ANRS CO22 HEPATHER French cohort and literature. 1000 Monte Carlo simulations of patient health states for each treatment strategy are used for probabilistic sensitivity analysis and 95% confidence intervals calculations. The results were expressed in cost per quality-adjusted life year (QALY) gained.
The mean age of patients in the HEPATHER French cohort was 59.6 years and 56% of them were men. 22.3% of patients had a F0 fibrosis stage (no fibrosis), 24.1% a F1 stage (portal fibrosis without septa), 7.1% a F2 stage (portal fibrosis with few septa), 21.4% a F3 stage (numerous septa without fibrosis) and 25% a F4 fibrosis stage (compensated cirrhosis). Among these HCV genotype 1 patients, 30% had severe renal impairment stage 4, 33% had a severe renal insufficiency stage 5 and 37% had terminal severe renal impairment stage 5 treated by dialysis.
Fixed-dose combination of direct-acting antiviral agents elbasvir and grazoprevir compared to no-treatment.
EBR/GZR increased the number of life years (6.3 years) compared to no treatment (5.1 years) on a lifetime horizon. The total number of QALYs was higher for the new treatment because of better utility on health conditions (6.2 versus 3.7 QALYs). The incremental cost-utility ratio (ICUR) was of €15,212 per QALY gained for the base case analysis.
This cost-utility model is an innovative approach that simultaneously looks at the disease evolution of chronic hepatitis C and chronic kidney disease. EBR/GZR without interferon and ribavirin, produced the greatest benefit in terms of life expectancy and quality-adjusted life years (QALY) in treatment-naïve or experienced patients with chronic hepatitis C genotype 1 and stage 4-5 chronic kidney disease including dialysis patients. Based on shape of the acceptability curve, EBR/GZR can be considered cost-effective at a willingness to pay of €20,000 /QALY for patients with renal insufficiency with severe and end-stage renal disease compared to no treatment.
评估 Elbasvir/grazoprevir（EBR/GZR）方案在伴有严重终末期肾病的基因型 1 慢性丙型肝炎病毒（HCV）感染患者中的成本效益，与未治疗相比。
本研究使用健康经济学模型来评估在法国环境中，用 Elbasvir-grazoprevir 方案治疗未经治疗和有治疗经验的慢性丙型肝炎患者的严重和终末期肾病的成本效益，这些患者患有严重终末期肾病。终生同质马尔可夫模型包括 40 个联合健康状态，包括丙型肝炎病毒和慢性肾脏病。模型参数来自一项多中心随机对照试验、ANRS CO22 HEPATHER 法国队列和文献。对于每种治疗策略，对 1000 名患者的健康状态进行蒙特卡罗模拟，以进行概率敏感性分析和 95%置信区间计算。结果以每获得质量调整生命年（QALY）的成本表示。
HEPATHER 法国队列中患者的平均年龄为 59.6 岁，其中 56%为男性。22.3%的患者为 F0 纤维化阶段（无纤维化），24.1%为 F1 阶段（无隔膜的门脉纤维化），7.1%为 F2 阶段（有少量隔膜的门脉纤维化），21.4%为 F3 阶段（无纤维化的多个隔膜），25%为 F4 纤维化阶段（代偿性肝硬化）。在这些 HCV 基因型 1 患者中，30%患有严重的肾功能损害 4 期，33%患有严重的肾功能不全 5 期，37%患有终末期严重肾功能损害 5 期，需要透析治疗。
直接作用抗病毒药物 Elbasvir 和 Grazoprevir 的固定剂量联合治疗与未治疗相比。
EBR/GZR 在终生范围内增加了生命年数（6.3 年），而未治疗则增加了 5.1 年。由于对健康状况的更好利用，新治疗的总 QALY 更高（6.2 与 3.7 QALY）。基于基础案例分析，增量成本效益比（ICUR）为每获得一个质量调整生命年（QALY）15212 欧元。
本成本效益模型是一种创新方法，同时考虑了慢性丙型肝炎和慢性肾脏病的疾病进展。对于未经治疗或有治疗经验的慢性丙型肝炎基因型 1 患者和包括透析患者在内的慢性肾脏病 4-5 期患者，无干扰素和利巴韦林的 EBR/GZR 在预期寿命和质量调整生命年（QALY）方面产生了最大的获益。基于可接受性曲线的形状，EBR/GZR 可以被认为在支付意愿为 20000 欧元/QALY 的情况下具有成本效益，对于伴有严重终末期肾病的肾功能不全患者，与未治疗相比。
