基于Markov模型对泛基因型直接抗病毒药物治疗慢性丙型肝炎的药物经济学评价

Economic Evaluation of the Pan-genotypic Direct-acting Antivirals in the Treatment of Chronic Hepatitis C in China Based on Markov Model

目的 评价已在中国上市的泛基因型直接抗病毒药物(DAAs)治疗方案与聚乙二醇干扰素(Peg-IFN)为基础的治疗方案用于慢性丙型肝炎(CHC)患者的经济性。方法 从中国医疗卫生体系视角出发,以中国初治CHC患者为目标人群,构建Markov模型。分别模拟非肝硬化和代偿性肝硬化CHC患者在不同治疗方案下获得的质量调整生命年(QALYs)和所花费的直接医疗成本,并计算增量成本-效用比(ICUR)。采用敏感性分析验证结果的稳健性。结果 对于非肝硬化CHC患者,与传统的聚乙二醇干扰素联合利巴韦林(PR)方案比较,3种泛基因型DAAs方案均增加了QALYs而显著降低了终身医疗成本,均为绝对优势方案。对于代偿性肝硬化患者,索磷布韦/维帕他韦方案的QALYs最高而终身治疗成本最低,依然是绝对优势方案。格卡瑞韦/哌仑他韦和索磷布韦联合达拉他韦方案与传统PR方案比较,ICUR分别为3 106.09元/QALY和80 843.45元/QALY;前者小于本研究设定的意愿支付阈值70 892元/QALY(2019年我国人均国内生产总值(GDP)),后者明显小于2019年国内人均GDP的3倍(212676元/QALY)。因此与传统PR方案比较,格卡瑞韦/哌仑他韦和索磷布韦联合达拉他韦方案亦具有显著的药物经济学优势。敏感性分析结果验证了基础分析结果的稳健性。以最具经济学优势的索磷布韦/维帕他韦为对照方案,通过成本-效用分析和阈值分析,测算若格卡瑞韦/哌仑他韦和索磷布韦联合达拉他韦方案达到同等经济性,格卡瑞韦/哌仑他韦、索磷布韦和达拉他韦需分别降价80.5%、80.0%和82.3%。结论 对于非肝硬化和代偿性肝硬化CHC患者,所有泛基因型DAAs治疗方案均具有显著的药物经济学优势,其中索磷布韦/维帕他韦最具成本-效用优势。

Objective To conduct economic evaluation of the pan-genotypic direct acting antiviral(DAAs) therapies which have been approved and launched in China versus peginterferon(Peg-IFN)-based regimen(PR) for chronic hepatitis C.Methods From the perspective of China’s medical and health system,Markov model was constructed with newly diagnosed chronic hepatitis C patients in China as the target population.To evaluate the quality-adjusted life years(QALYs) and direct medical costs for noncirrhotic patients and compensated cirrhotic patients respectively,and to further calculate incremental cost-utility ratio(ICUR)of different regimens.Sensitivity analysis was used to verify the robustness of the results.Results For patients with noncirrhotic chronic hepatitis C,compared with conventional peginterferon combined with ribavirin regimen(PR),the three pangenotypes of DAAs increased QALYs and significantly reduced lifetime medical costs,all of which were absolute advantages.For patients with compensative cirrhosis,the sofosbuvir/velpatasvir regimen remains the dominant regimen with the highest QALYs and lowest lifetime treatment cost.The incremental cost-utility ratio(ICUR) of glecaprevir/pibrentasvir and sofosbuvir combined with daclatavir were 3 106.09 yuan/QALY and 80 843.45 yuan/QALY respectively compared with traditionnal PR regimen.The former is less than the willing to pay threshold of 70 892 yuan/QALY set in this study(1 times of GDP per capita in 2019),while the latter is much less than 3 times of GDP per capita in 2019(212 676 yuan/QALY).Therefore,compared with the traditional PR regimen,the regimen of geccareavir/perentavir and sofosbuvir combined with dalatavir also has significant pharmacoeconomic advantages.The sensitivity analysis results verified the robustness of the basic analysis results.Sofosbuvir/velpatasvir which had the most economic advantage was used as the control scheme,through the cost-utility analysis and threshold analysis,we calculated that glecaprevir/pibrentasvir,sofosbuvir and daclatavir were needed to reduce their prices by 80.5%,80.0% and 82.3% respectively,assuming that both glecaprevir/pibrentasvir and sofosbuvir combined with daclatavir regime achieved the equal economy.Conclusion For the patients with noncirrhotic and compensatory cirrhosis chronic hepatitis C,all pan-genotypic DAAs have significant pharmacoeconomic advantage,while sofosbuvir/velpatasvir has the most cost-utility advantage among them.