重组人血小板生成素治疗原发免疫性和脓毒症相关性血小板减少症的快速卫生技术评估

Rapid Health Technology Assessment of rhTPO in the Treatment of ITP and SAT

目的快速评价重组人血小板生成素(rhTPO)治疗原发免疫性血小板减少症(ITP)和脓毒症相关性血小板减少症(SAT)的有效性、安全性和经济性。方法采用计算机检索PubMed、The Cochrane Library、中国知网和万方数据库中相关文献,检索时间为自建库起至2021年11月15日。由2名评价者根据纳入与排除标准独立筛选文献及提取数据,对结果进行定性分析,使用AMSTAR(a measurement tool to assess systematic reviews)和CHEERS(Consolidated Health Economic Evaluation Reporting Stanards)量表分别评价系统评价/Meta分析及药物经济学研究的质量。结果共纳入9篇系统评价/Meta分析和4篇药物经济学研究。对于成人ITP,与单用达那唑(或糖皮质激素)相比,rhTPO联用方案能显著提高血小板恢复的有效率[OR=3.79,95%CI(2.50,5.73),P<0.01]和总反应率[RR=1.46,95%CI(1.27,1.66),P<0.00001],但显效率[OR=2.95,95%CI(1.37,6.37),P=0.06]、持续有效率[RR=1.77,95%CI(0.94,3.33),P=0.08]和不良反应发生率[OR=3.56,95%CI(0.85,14.95),P=0.08]无显著差异;与地塞米松、利妥昔单抗、人免疫球蛋白(两联或三联)相比,rhTPO联合糖皮质激素均能显著改善长期持久应答[RR=2.01,95%CI(0.75,5.40);RR=11.45,95%CI(2.07,63.36);RR=1.95,95%CI(0.60,6.38)]和早期总体应答[RR=1.39,95%CI(0.97,2.01);RR=1.84,95%CI(1.06,3.19);RR=1.10,95%CI(0.65,1.88)];但rhTPO联合利妥昔单抗对提高血小板的总反应率不如艾曲泊帕[RR=0.23,95%CI(0.07,0.83)]和罗米司亭[RR=0.26,95%CI(0.07,0.98)],且不良反应较大。对于儿童ITP,与单用糖皮质激素相比,单用rhTPO能显著增加ITP患儿的有效率[RR=1.46,95%CI(1.05,1.79),P=0.02],且不良反应发生率显著下降[RR=0.39,95%CI(0.18,0.81),P=0.01]。对于成人SAT,与安慰剂、单用传统抗菌药物、传统抗菌药物+人免疫球蛋白相比,单用rhTPO总体能改善重症监护室住院时间[SMD=-0.49,95%CI(-0.85,-0.13),P=0.008;SMD=−0.31,95%CI(−0.56,−0.00),P=0.02;SMD=-0.02,95%CI(-0.35,0.13),P=0.90]和第7天外周血小板计数[SMD=2.16,95%CI(1.13,3.19),P<0.0001;SMD=2.61,95%CI(1.28,3.94),P<0.001;SMD=0.86,95%CI(0.54,1.17),P<0.001);血小板[SMD=-1.29,95%CI(-1.65,-0.93),P<0.00001;SMD=-1.47,95%CI(-1.99,-0.96),P<0.001;SMD=-0.65,95%CI(-0.89,-0.40),P<0.001],血浆[SMD=-2.08,95%CI(-3.53,-0.64),P=0.005;SMD=-2.35,95%CI(-4.14,-0.56),P=0.01;SMD=-0.61,95%CI(-0.85,-0.36),P<0.001]和红细胞[SMD=-1.33,95%CI(-2.22,-0.44),P=0.003;SMD=-1.42,95%CI(-2.51,-0.34),P=0.01;SMD=-0.47,95%CI(-0.72,-0.23),P<0.001]的输注量。此外,与糖皮质激素+人免疫球蛋白相比,rhTPO+糖皮质激素治疗ITP更具成本-效果优势;但与单用利妥昔单抗相比,rhTPO+利妥昔单抗则不具有成本-效果优势。结论rhTPO治疗成人和儿童ITP的有效性和安全性均较好,且对成人SAT的有效性也较好。rhTPO联用糖皮质激素治疗成人ITP具有一定的经济性,但联用利妥昔单抗时则缺乏经济学优势。

Objective To assess the effectiveness,safety and economy of recombinant human thrombopoietin(rhTPO)in the treatment of primary immune thrombocytopenia(ITP)and sepsis-associated thrombocytopenia(SAT)rapidly.Methods The related studies in the PubMed,The Cochrane Library,CNKI and WanFang databases from the inception to November 15,2021 were searched by the computer.The studies were screened and the data were extracted independently by two reviewers according to the inclusion and exclusion criteria,and the results were analyzed qualitatively.The quality of the systematic review/Meta-analysis and pharmacoeconomic study was assessed by the AMSTAR(a measurement tool to assess systematic reviews)and CHEERS(Consolidated Health Economic Evaluation Reporting Stanards)scales respectively.Results Nine systematic reviews/Meta-analyses and four pharmacoeconomic studies were included.For the treatment of ITP in adults,compared with danazol(or glucocorticoid)alone,rhTPO combined with danazol(or glucocorticoid)could significantly improve the effective rate[OR=3.79,95%CI(2.50,5.73),P<0.01]and the total response rate of platelet recovery[RR=1.46,95%CI(1.27,1.66),P<0.00001],while the explicit effective rate[OR=2.95,95%CI(1.37,6.37),P=0.06],continuous effective rate[RR=1.77,95%CI(0.94,3.33),P=0.08]and the incidence of adverse reactions[OR=3.56,95%CI(0.85,14.95),P=0.08]of rhTPO combined with danazol(or glucocorticoid)were similar to those of danazol(or glucocorticoid)alone.Compared with dexamethasone,rituximab and human immunoglobulin(double or triple),rhTPO combined with glucocorticoid could significantly improve the long-term sustained response[RR=2.01,95%CI(0.75,5.40);RR=11.45,95%CI(2.07,63.36);RR=1.95,95%CI(0.60,6.38)]and the early overall response[RR=1.39,95%CI(0.97,2.01);RR=1.84,95%CI(1.06,3.19);RR=1.10,95%CI(0.65,1.88)].However,rhTPO combined with rituximab could not improve the total response rate of platelet as eltrombopag[RR=0.23,95%CI(0.07,0.83)]and romiplostim[RR=0.26,95%CI(0.07,0.98)],and the incidence of adverse reactions of rhTPO combined with rituximab was higher.For the treatment of ITP in children,compared with glucocorticoid alone,rhTPO alone could significantly increase the effective rate of children with ITP[RR=1.46,95%CI(1.05,1.79),P=0.02],and it could also significantly decrease the incidence of adverse reactions[RR=0.39,95%CI(0.18,0.81),P=0.01].For the treatment of SAT in adults,compared with placebo,traditional antibiotics alone and traditional antibiotics+human immunoglobulin,rhTPO alone could reduce the length of stay in intensive care unit[SMD=-0.49,95%CI(-0.85,-0.13),P=0.008;SMD=-0.31,95%CI(-0.56,-0.00),P=0.02;SMD=-0.02,95%CI(-0.35,0.13),P=0.90],increase the peripheral platelet count on the seventh day[SMD=2.16,95%CI(1.13,3.19),P<0.0001;SMD=2.61,95%CI(1.28,3.94),P<0.001;SMD=0.86,95%CI(0.54,1.17),P<0.001],and decrease the infusion volume of platelets[SMD=-1.29,95%CI(-1.65,-0.93),P<0.00001;SMD=-1.47,95%CI(-1.99,-0.96),P<0.001;SMD=-0.65,95%CI(-0.89,-0.40),P<0.001],plasma[SMD=-2.08,95%CI(-3.53,-0.64),P=0.005;SMD=-2.35,95%CI(-4.14,-0.56),P=0.01;SMD=-0.61,95%CI(-0.85,-0.36),P<0.001]and red blood cells[SMD=-1.33,95%CI(-2.22,-0.44),P=0.003;SMD=-1.42,95%CI(-2.51,-0.34),P=0.01;SMD=-0.47,95%CI(-0.72,-0.23),P<0.001].In addition,compared with glucocorticoid+human immunoglobulin,rhTPO+glucocorticoid was more cost-effective in the treatment of ITP.However,compared with rituximab alone,rhTPO+rituximab had no cost-effectiveness advantage.Conclusion The drug of rhTPO is effective and safe in the treatment of ITP in adults and children,and it is effective in the treatment of SAT in adults.The scheme of rhTPO combined with glucocorticoid has a certain economic advantage in the treatment of ITP in adults,but rhTPO lacks economic advantage when combined with rituximab.