艾曲波帕联合用药治疗成人原发免疫性血小板减少症的有效性及安全性系统评价

Effect and safety of eltrombopag combined with other drugs treatment for adult primary immune thrombocytopenia:A systematic review

目的:系统评价艾曲波帕联合用药治疗成人原发免疫性血小板减少症(ITP)的有效性与安全性。方法:检索Medline,PubMed,Cochrane图书馆、Embase、知网期刊数据库、万方数据库,纳入以艾曲波帕联合其他药物为干预措施治疗成人ITP的文献,检索时间从建库至2020年12月,利用SPSS 25.0软件进行数据分析。结果:共纳入8篇文献,286例患者。1篇文献报道了艾曲波帕联合利妥昔单抗的有效率显著高于单用艾曲波帕(75.0%vs 41.7%,P<0.05)。2篇文献报道了艾曲波帕联合重组人血小板生成素(rhTPO)的有效率显著高于单用rhTPO(94.4%vs 75.0%,P<0.05;78.1%vs 56.3%,P<0.05)。1篇文献报道了艾曲波帕联合地塞米松的有效率显著高于单用地塞米松(94.4%vs 81.5%,P<0.05)。上述4篇文献艾曲波帕联合用药与单药比较,不良事件发生率差异均无统计学意义(P>0.05)。2篇文献报道了艾曲波帕联合地塞米松的方案,但无对照组,有效率分别为97.8%、100%,其中1篇不良事件发生率为51.1%。1篇文献报道了艾曲波帕联合地塞米松及利妥昔单抗的三联方案,但无对照组,有效率为100%,不良事件发生率为30.8%。1篇文献报道了艾曲波帕联合硫唑嘌呤的有效率与环孢素联合达那唑比较,差异无统计学意义(69.6%vs 73.9%,P>0.05),但前者不良事件发生率显著低于后者(34.8%vs 69.6%,P<0.05)。进一步比较分析显示,艾曲波帕联合地塞米松有效率(97.3%)显著高于艾曲波帕联合硫唑嘌呤(69.9%)(P<0.001)、艾曲波帕联合利妥昔单抗(75.0%)(P=0.008)、艾曲波帕联合rhTPO(84.0%)(P=0.006),但艾曲波帕联合rhTPO的不良事件发生率(16.0%)显著低于艾曲波帕联合地塞米松(52.4%)(P<0.001)。结论:与单药相比较,艾曲波帕联合用药的有效性显著提高,安全性没有差异。艾曲波帕联合地塞米松有效率显著高于联合硫唑嘌呤、利妥昔单抗以及rhTPO,但安全性不及艾曲波帕联合rhTPO。

Objective: To evaluate the efficacy and safety of eltrombopag combined with other drugs for the treatment of primary immune thrombocytopenia(ITP). Methods: Medline, Pubmed, Cochrane Library, Embase, CNKI and Wanfang database were searched until December 2020 about studies of eltrombopag combined with other drugs on the treatment of ITP disease. Statistical analysis was performed with SPSS software version 25.0. Results: Eight studies involving 286 patients were included. One study showed that response rate of eltrombopag+rituximab was significantly higher than that of eltrombopag(75.0% vs 41.7%, P<0.05). Two studies showed that response rates of eltrombopag+recombinant human thrombopoietin(rhTPO) were significantly higher than those of rhTPO(94.4% vs 75.0%, P<0.05, 78.1% vs 56.3%, P<0.05). One study showed that response rate of eltrombopag+dexamethasone was significantly higher than that of dexamethasone(94.4% vs 81.5%, P<0.05). Four studies above-mentioned showed that adverse event rates of eltrombopag combined with other drugs had no significant difference compared with single drug(P>0.05).Two studies with no control group showed that response rates of eltrombopag+dexamethasone were 97.8% and 100% respectively, and one study showed that adverse event rate of eltrombopag+dexamethasone was 51.1%. One study showed trigeminy regimen of eltrombopag+dexamethasone+rituximab, the response rate was 100% and adverse event rate was 30.8%. One study showed that response rates of eltrombopag+azathioprine and cyclosporine+dazol were 69.6% and 73.9% respectively, with no significant difference(P>0.05), but adverse event rate of the former was lower than the latter(34.8% vs 69.6%, P<0.05). Further analysis showed significant differences among the regimen of eltrombopag combined with other drugs. The response rate of eltrombopag+dexamethasone(97.3%) was significantly higher than eltrombopag+azathioprine(69.9%)(P<0.001), eltrombopag+rituximab(75.0%)(P=0.008), eltrombopag+rhTPO(84.0%)(P=0.006). The adverse event rate of eltrombopag+rhTPO(16.0%) was significantly lower than that of eltrombopag+dexamethasone(52.4%)(P<0.001). Conclusion: Compared with single drug, the response rates of eltrombopag combined with other drugs are significantly higher, the adverse event rates have no significant difference. The response rate of eltrombopag+dexamethasone is significantly higher than that of eltrombopag+rituximab, eltrombopag+rhTPO, but the adverse event rate is significantly higher than that of eltrombopag+rhTPO.