传统与新型抗癫痫药物在成人癫痫患者中的保留率及相关危险因素交互作用研究
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摘要
目的探讨6种常用新型和传统抗癫痫药物在成人癫痫患者中的保留率、有效性以及影响药物保留的相关危险因素的交互作用。方法纳入2013年9月～2016年8月我院226例新确诊的成人癫痫患者,根据用药分为6组,即卡马西平组、丙戊酸钠组、托吡酯组、奥卡西平组、拉莫三嗪组、左乙拉西坦组,随访记录各组癫痫发作情况、不良反应以及终点事件。采用Kaplan-Meire生存曲线和Cox比例风险模型等进行相关统计学分析。结果 6种药物中12个月保留率分别为,新型抗癫痫药物:左乙拉西坦(83.3%)、奥卡西平(66.7%)、拉莫三嗪(66.7%)、托吡酯(75.0%),传统抗癫痫药物:卡马西平(64.1%)、丙戊酸钠(65.7%)。新型与传统抗癫痫药物12个月保留率无统计学差异(P>0.05),但左乙拉西坦明显优于传统抗癫痫药物(P<0.05)。6种抗癫痫药物之间及传统与新型药物之间控制率无统计学差异(P>0.05)。停药原因新型药物主要为疗效差(37.1%),传统药物为副反应发生率高(32.4%)。多因素Logistic分析显示,全面性癫痫类型是停药的保护性因素(RR=0.448,95%CI 0.272～0.736),而脑卒中(病因)与年龄(≥50岁)的交互作用是导致停药的危险因素(RR=3.644,95%CI 1.288～7.310)。结论新型与传统抗癫痫药物保留率相似,但是新型抗癫痫药物中左乙拉西坦的保留率却明显高于传统抗癫痫药物中的卡马西平、丙戊酸钠。6种抗癫痫药物之间及传统与新型药物有效性无差异。脑卒中(癫痫病因)与年龄(≥50岁)的交互作用是导致停药的独立危险因素,全面性癫痫是停药的保护性因素。
Objective To investigate the retention rate and discontinuation factors of traditional and new antiepileptic drugs in adult epileptic. Methods According to the ILAE guidelines, 226 newly diagnosed adult epileptic were prescribed with carbamazepine(CBZ), valproate(VPA), lamotrigine(LTG), topiramate(TPM), oxcarbazepine(OXC) or levetiracetam(LEV) as monotherapy from Sep 2013 to Aug 2016 in our hospital. Seizures frequency, adverse events and termination events were recorded though phone calls or interviews every 1～2 months. Used Kaplan-Meire survival curve and Cox proportional hazards model for statistical analysis. Results 12 month-retention rate of these antiepileptic drugs:LEV(83.3%), OXC(66.7%), LTG(66.7%), TPM(75.0%), CBZ(64.1%), VPA(65.7%). Compared with traditional antiepileptic drugs, the retention rate of new antiepileptic drugs had no significant differences(P>0.05),but the rate of levetiracetam was significantly higher than the traditional antiepileptic drugs. There was no significant difference of effectiveness among the six antiepileptic drugs. The reasons of drug withdrawal were mainly about poor efficacy for new antiepileptic drugs(37.1%) and adverse reaction for traditional drugs(32.4%). The cross action between stroke and age(≥50) was the risk factors of drug withdrawal(RR=3.644,95%CI 1.288～7.310); meanwhile the generalized seizure was a protective factor of drug withdrawal(RR=0.448,95%CI 0.272～0.736). Conclusion The total retention rate of the new antiepileptic drugs is similar to that of the traditional antiepileptic drugs, but levetiracetam has a higher retention rate than the traditional antiepileptic drugs. There is no significant difference in efficacy among the six antiepileptic drugs and between the traditional and new antiepileptic drugs. The cross action between stroke and age( ≥50) is the risk factor of drug withdrawal, meanwhile the generalized seizure is a protective factor of drug withdrawal.
Objective To investigate the retention rate and discontinuation factors of traditional and new antiepileptic drugs in adult epileptic. Methods According to the ILAE guidelines, 226 newly diagnosed adult epileptic were prescribed with carbamazepine(CBZ), valproate(VPA), lamotrigine(LTG), topiramate(TPM), oxcarbazepine(OXC) or levetiracetam(LEV) as monotherapy from Sep 2013 to Aug 2016 in our hospital. Seizures frequency, adverse events and termination events were recorded though phone calls or interviews every 1～2 months. Used Kaplan-Meire survival curve and Cox proportional hazards model for statistical analysis. Results 12 month-retention rate of these antiepileptic drugs:LEV(83.3%), OXC(66.7%), LTG(66.7%), TPM(75.0%), CBZ(64.1%), VPA(65.7%). Compared with traditional antiepileptic drugs, the retention rate of new antiepileptic drugs had no significant differences(P>0.05),but the rate of levetiracetam was significantly higher than the traditional antiepileptic drugs. There was no significant difference of effectiveness among the six antiepileptic drugs. The reasons of drug withdrawal were mainly about poor efficacy for new antiepileptic drugs(37.1%) and adverse reaction for traditional drugs(32.4%). The cross action between stroke and age(≥50) was the risk factors of drug withdrawal(RR=3.644,95%CI 1.288～7.310); meanwhile the generalized seizure was a protective factor of drug withdrawal(RR=0.448,95%CI 0.272～0.736). Conclusion The total retention rate of the new antiepileptic drugs is similar to that of the traditional antiepileptic drugs, but levetiracetam has a higher retention rate than the traditional antiepileptic drugs. There is no significant difference in efficacy among the six antiepileptic drugs and between the traditional and new antiepileptic drugs. The cross action between stroke and age( ≥50) is the risk factor of drug withdrawal, meanwhile the generalized seizure is a protective factor of drug withdrawal.
引文
1 Organization WH.EN Regional declarations for Epilepsy[J].2014
2 Brodie MJ,Barry SJE,Bamagous GA,et al.Patterns of treatment response in newly diagnosed epilepsy[J].Neurology,2012,78(20):1548-1554
3 Glauser T,Ben‐Menachem E,Bourgeois B,et al.Updated ILAEevidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes[J].Epilepsia,2013,54(3):551-563
4 Ben-Menachem E,Sander JW,Privitera M,et al.Measuring outcomes of treatment with antiepileptic drugs in clinical trials[J].Epilepsy&Behavior,2010,18(1):24-30
5 Glauser T,Ben‐Menachem E,Bourgeois B,et al.ILAE treatment guidelines:evidence‐based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes[J].Epilepsia,2006,47(7):1094-1120
6 Dreyer NA,Garner S.Registries for Robust Evidence[J].Jama-JAm Med Assoc,2009,302(7):790-791
7 Marson AG,Williamson PR,Clough H,et al.Carbamazepine versus valproate monotherapy for epilepsy:a meta-analysis[J].Epilepsia,2002,43(5):505-513
8 Stephen LJ,Sills GJ,Leach JP,et al.Sodium valproate versus lamotrigine:A randomised comparison of efficacy,tolerability and effects on circulating androgenic hormones in newly diagnosed epilepsy[J].Epilepsy Research,2007,75(2-3):122-129
9 Mills JK,Lewis TG,Mughal K,et al.Retention rate of Clobazam,Topiramate and Lamotrigine in children with intractable epilepsies at 1 year-Seizure-European Journal of Epilepsy[J].Seizure,2011,20(5):402-405
10 Hu Y,Lu Y,Yu W,et al.Long-term retention rate of topiramate as initial monotherapy in Chinese patients with newly diagnosed epilepsy:a prospective,observational study[J].Epilepsy Research,2010,90(3):278-284
11 Rainesalo S,Peltola J,Auvinen A,et al.Retention rate of oxcarbazepinemonotherapy in an unselected population of adult epileptics[J].Seizure,2005,14(1):72-74
12 Droz-Perroteau C,Dureau-Pournin C,Vespignani H,et al.The EULEV cohort study:rates of and factors associated with continuation of levetiracetam after 1 year[J].British Journal of Clinical Pharmacology,2011,71(1):121-127
13 Pohlmanneden B.Comparative effectiveness of levetiracetam,valproate and carbamazepine among elderly patients with newly diagnosed epilepsy:subgroup analysis of the randomized,unblinded KOMET study[J].BMC Neurology,2016,16(1):149
14 Nolan SJ,Smith CT,Weston J,et al.Lamotrigine versus carbamazepine monotherapy for epilepsy:an individual participant data review[M]//The Cochrane Library.John Wiley&Sons,Ltd,2016
15 Lee SK.Old versus new:why do we need new antiepileptic drugs?[J].Epilepsy Research,2014,4(2):39
16 Wieshmann UC,Baker G.Efficacy and tolerability of anti-epileptic drugs-an internet study[J].Acta Neurdogica Scandinavirca,2017,135(5):533-539
17 Hu Y,Huang Y,Quan F,et al.Comparison of the retention rates between carbamazepine and valproate as an initial monotherapy in Chinese patients with partial seizures:A ten-year follow-up,observational study[J].Seizure,2011,20(3):208-213
18 Lhatoo SD,Wong IC,Polizzi G,et al.Long-term retention rates of lamotrigine,gabapentin,and topiramate in chronic epilepsy[J].Epilepsia,2000,41(1):1592-1596
19 Brodie MJ,Kwan P.Epilepsy in elderly people[J].BMJ,2005,331(7528):1317-1322
20 Si Y,Liu L,Hu J,et al.Etiologic features of newly diagnosed epilepsy:hospital-based study of 892 consecutive patients in West China[J].Seizure,2012,21(1):40
21贾建平,陈生弟.神经病学[M].7版.北京:人民卫生出版社,2013
2 Brodie MJ,Barry SJE,Bamagous GA,et al.Patterns of treatment response in newly diagnosed epilepsy[J].Neurology,2012,78(20):1548-1554
3 Glauser T,Ben‐Menachem E,Bourgeois B,et al.Updated ILAEevidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes[J].Epilepsia,2013,54(3):551-563
4 Ben-Menachem E,Sander JW,Privitera M,et al.Measuring outcomes of treatment with antiepileptic drugs in clinical trials[J].Epilepsy&Behavior,2010,18(1):24-30
5 Glauser T,Ben‐Menachem E,Bourgeois B,et al.ILAE treatment guidelines:evidence‐based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes[J].Epilepsia,2006,47(7):1094-1120
6 Dreyer NA,Garner S.Registries for Robust Evidence[J].Jama-JAm Med Assoc,2009,302(7):790-791
7 Marson AG,Williamson PR,Clough H,et al.Carbamazepine versus valproate monotherapy for epilepsy:a meta-analysis[J].Epilepsia,2002,43(5):505-513
8 Stephen LJ,Sills GJ,Leach JP,et al.Sodium valproate versus lamotrigine:A randomised comparison of efficacy,tolerability and effects on circulating androgenic hormones in newly diagnosed epilepsy[J].Epilepsy Research,2007,75(2-3):122-129
9 Mills JK,Lewis TG,Mughal K,et al.Retention rate of Clobazam,Topiramate and Lamotrigine in children with intractable epilepsies at 1 year-Seizure-European Journal of Epilepsy[J].Seizure,2011,20(5):402-405
10 Hu Y,Lu Y,Yu W,et al.Long-term retention rate of topiramate as initial monotherapy in Chinese patients with newly diagnosed epilepsy:a prospective,observational study[J].Epilepsy Research,2010,90(3):278-284
11 Rainesalo S,Peltola J,Auvinen A,et al.Retention rate of oxcarbazepinemonotherapy in an unselected population of adult epileptics[J].Seizure,2005,14(1):72-74
12 Droz-Perroteau C,Dureau-Pournin C,Vespignani H,et al.The EULEV cohort study:rates of and factors associated with continuation of levetiracetam after 1 year[J].British Journal of Clinical Pharmacology,2011,71(1):121-127
13 Pohlmanneden B.Comparative effectiveness of levetiracetam,valproate and carbamazepine among elderly patients with newly diagnosed epilepsy:subgroup analysis of the randomized,unblinded KOMET study[J].BMC Neurology,2016,16(1):149
14 Nolan SJ,Smith CT,Weston J,et al.Lamotrigine versus carbamazepine monotherapy for epilepsy:an individual participant data review[M]//The Cochrane Library.John Wiley&Sons,Ltd,2016
15 Lee SK.Old versus new:why do we need new antiepileptic drugs?[J].Epilepsy Research,2014,4(2):39
16 Wieshmann UC,Baker G.Efficacy and tolerability of anti-epileptic drugs-an internet study[J].Acta Neurdogica Scandinavirca,2017,135(5):533-539
17 Hu Y,Huang Y,Quan F,et al.Comparison of the retention rates between carbamazepine and valproate as an initial monotherapy in Chinese patients with partial seizures:A ten-year follow-up,observational study[J].Seizure,2011,20(3):208-213
18 Lhatoo SD,Wong IC,Polizzi G,et al.Long-term retention rates of lamotrigine,gabapentin,and topiramate in chronic epilepsy[J].Epilepsia,2000,41(1):1592-1596
19 Brodie MJ,Kwan P.Epilepsy in elderly people[J].BMJ,2005,331(7528):1317-1322
20 Si Y,Liu L,Hu J,et al.Etiologic features of newly diagnosed epilepsy:hospital-based study of 892 consecutive patients in West China[J].Seizure,2012,21(1):40
21贾建平,陈生弟.神经病学[M].7版.北京:人民卫生出版社,2013