依洛尤单抗治疗高胆固醇血症有效性、安全性和经济性的快速卫生技术评估

Effectiveness,Safety and Economy of Evolocumab in the Treatment of Hypercholesterolemia:A Rapid Health Technology Assessment

目的:快速评价依洛尤单抗治疗高胆固醇血症的有效性、安全性和经济性,旨在为临床药物选择和决策提供循证依据。方法:计算机检索PubMed、Cochrane图书馆、中国知网、万方数据和卫生技术评估(HTA)相关官方网站,收集依洛尤单抗单用或联合标准治疗方案对比标准治疗方案或安慰剂或依折麦布用于高胆固醇血症的HTA报告、系统评价/Meta分析和药物经济学研究,检索时限均为建库/建站起至2020年1月。在筛选文献、提取资料的基础上,分别采用HTA checklist、系统评价评估测量工具AMSTAR-2量表、综合卫生经济评价报告标准量表评价纳入HTA报告、系统评价/Meta分析和药物经济学研究的文献质量,并对有效性、安全性结果进行定量描述,对经济学评价结果进行定性描述。结果:共纳入13篇文献,其中6篇为Meta分析文献、7篇为经济学文献;Meta分析文献质量偏低,经济学研究质量较好。在有效性方面,与安慰剂/依折麦布比较,依洛尤单抗可显著降低患者低密度脂蛋白胆固醇、总胆固醇、三酰甘油、极低密度脂蛋白胆固醇水平以及心血管事件、心肌梗死、冠状动脉缺血、卒中发生率,增加高密度脂蛋白胆固醇水平(P<0.05);而两者不稳定性心绞痛住院风险、心脏死亡率或心血管疾病死亡率比较,差异均无统计学意义(P>0.05)。在安全性方面,依洛尤单抗任一不良事件发生率、任一治疗紧急不良事件发生率、背部疼痛发生率、肌肉骨骼和结缔组织疾病合并发病率与安慰剂比较,差异均无统计学意义(P>0.05)。在经济性方面,在标准治疗方案基础上加用依洛尤单抗,对血脂仍不达标的高危动脉粥样硬化性心血管疾病(ASCVD)患者具有一定的成本-效果优势。结论:依洛尤单抗对于高胆固醇血症患者的有效性和安全性均较好;对于经标准治疗方案治疗后血脂仍不达标的高危ASCVD患者,该药具有一定的经济性,可作为备选方案。

OBJECTIVE:To rapidly evaluate the effectiveness,safety and economy of evolocumab in the treatment of hypercholesterolemia so as to provide evidence-based reference for clinical drug selection and decision.METHODS:Retrieved from PubMed,Cochrane Library,CNKI,Wanfang database and HTA relative official website,HTA reports,systematic evaluation/Meta-analysis and pharmacoeconomic studies about evolocumab alone or combined with standard plan versus standard plan or placebo or ezetimibe in the treatment of hypercholesterolemia were collected during the inception to Jan.2020.Based on literature screening and data extraction,HTA checklist,system evaluation measurement tool AMSTAR-2 scale,comprehensive healthy economic evaluation report standard scale were used to evaluate the quality of included HTA reports,systematic evaluation/Meta-analysis and pharmacoeconomic literatures.Quantitative description was performed for effectiveness and safety results,and qualitative description was performed for economic evaluation results.RESULTS:A total of 13 literatures were included,involving6 Meta-analysis and 7 economic studies.The quality of Meta-analysis literatures was low,and the quality of economic research was good.In terms of effectiveness,compared with placebo or ezetimibe,evolocumab significantly reduced the levels of LDL-C,TC,TG and VLDL-C,the incidence of cardiovascular events,myocardial infarction,coronary ischemia and stroke,while increased the level of HDL-C(P<0.05).There was no statistical significance in the risk of hospitalization,cardiac mortality or cardiovascular disease mortality in patients with unstable angina pectoris between placebo and evolocumab(P>0.05).In terms of safety,there was no significant difference in the incidence of any adverse events,any treatment emergency adverse events and back pain,musculoskeletal and connective tissue diseases between evolocumab and placebo(P>0.05).In terms of economy,additional use of evolocumab,based on standard plan,had a cost-effectiveness advantage for patients with high-risk atherosclerotic cardiovascular disease(ASCVD)whose blood lipids were still not up to standard.CONCLUSIONS:Evolocumab has good effectiveness and safety in the treatment of hypercholesterolemia.For high-risk patients with ASCVD whose blood lipids are still not up to standard after standard plan,evolocumab has certain economy and can be used as an alternative.