第三代与第二代抗癫痫药物添加治疗局灶性癫痫疗效与安全性比较的Meta分析  

EFFICACY AND SAFETY OF THIRD-GENERATION VERSUS SECOND-GENERATION ANTIEPILEPTIC DRUGS AS ADJUNCTIVE THERAPY FOR FOCAL EPILEPSY:A META-ANALYSIS

作　　者：陈文贤 王雁[1] 程永红[1] CHEN Wenxian;WANG Yan;CHENG Yonghong(Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China)

机构地区：[1]青岛大学附属医院神经内科,山东青岛266003

出　　处：《精准医学杂志》2021年第2期104-109,113,共7页Journal of Precision Medicine

基　　金：青岛市民生科技计划项目(15-9-2-92-nsh)。

摘　　要：目的比较第三代抗癫痫药物拉考沙胺(LCM)、吡仑帕奈(PER)与第二代抗癫痫药物奥卡西平(OXC)、左乙拉西坦(LEV)添加治疗局灶性癫痫效果与安全性。方法检索PubMed、Embase、Cochrane library、中国知网、维普数据库和万方数据库,检索时间为1969年7月—2020年3月。选择LCM、PER、OXC、LEV这4种抗癫痫药物的随机对照试验(RCT)进行Meta分析。主要的结局指标为患者发作频率降低≥50%、完全控制率、总不良反应事件、因不良反应退出事件、严重不良反应事件。采用Revman 5.3统计软件与ITC软件进行数据处理。结果共纳入随机对照试验17篇,6029例患者。间接比较中各组间患者使用不同剂量OXC、LEV与LCM的疗效比较差异无统计学意义(P>0.05)。间接比较中各组间患者使用PER(12 mg)的完全控制率显著低于使用LEV(3000 mg)(RD=-0.05,95%CI=-0.09~-0.01,P<0.05)。间接比较中各组间患者使用LCM(400 mg)、PER(12 mg)的因不良反应退出率均显著高于使用LEV(3000 mg)(RD=0.09,95%CI=0.04~0.14,P<0.05;RD=0.19,95%CI=0.07~0.19,P<0.05)。通过对亚裔患者用药进一步亚组分析,间接比较中各组间患者使用LCM与LEV的疗效及安全性差异无统计学意义(P>0.05)。结论间接对比结果表明,OXC、LEV的疗效不劣于LCM、PER。LEV(3000 mg)安全性优于LCM(400 mg)、PER(12 mg)。第三代抗癫痫药物(LCM、PER)的疗效与安全性未能超越第二代抗癫痫药物(OXC、LEV)。Objective To investigate the efficacy and safety of the third-generation antiepileptic drugs lacosamide(LCM)and perampanel(PER)versus the second-generation antiepileptic drugs oxcarbazepine(OXC)and levetiracetam(LEV)as adjunctive therapy for focal epilepsy.Methods PubMed,Embase,Cochrane Library,CNKI,VIP,and Wanfang Data were searched for related articles published from July 1969 to March 2020.A meta-analysis was performed for the randomized controlled trials(RCTs)of the four antiepileptic drugs LCM,PER,OXC,and LEV.Main outcome measures included a reduction of≥50%in seizure frequency,complete control rate,total adverse events,withdrawal rate due to adverse events,and serious adverse events.RevMan 5.3 and ITC software were used for data processing.Results A total of 17 RTCs were included,with 6029 patients in total.Indirect comparison showed no significant difference in efficacy between OXC,LEV,and LCM at different doses(P>0.05).The patients treated with PER(12 mg)had a significantly lower complete control rate than those treated with LEV(3000 mg)(risk difference(RD)=-0.05,95%CI=-0.09--0.01,P<0.05).The patients treated with LCM(400 mg)and PER(12 mg)had a significantly higher withdrawal rate due to adverse events than those treated with LEV(3000 mg)(LCM vs LEV:RD=0.09,95%CI=0.04-0.14,P<0.05;PER vs LEV:RD=0.19,95%CI=0.07-0.19,P<0.05).A further subgroup analysis was performed for medications used in Asian patients,and the results showed that there were no significant differences in efficacy and safety between the patients treated with LCM and those treated with LEV(P>0.05).Conclusion Indirect comparison shows that OXC and LEV are not inferior to LCM and PER in terms of efficacy.LEV(3000 mg)has better safety than LCM(400 mg)and PER(12 mg).The third-generation antiepileptic drugs LCM and PER cannot exceed the second-generation antiepileptic drugs LEV and OXC in the aspects of efficacy and safety.

关 键 词：抗惊厥药 癫痫 部分性 拉考沙胺 吡仑帕奈 奥卡西平 左乙拉西坦 治疗结果 不良反应 META分析 

分 类 号：R742.1[医药卫生—神经病学与精神病学]