新型抗癫痫药单药治疗新诊断癫痫患者保留率的对比研究

发布时间：2018-08-13 12:39

【摘要】：背景:癫痫是神经系统的常见病和多发病,长期药物治疗是目前公认的主要措施,新型抗癫痫药因其广泛的抗痫谱、良好的发作控制率及较少的不良反应发生率优势在临床得到广泛应用,已有多项研究证实了其有效性及耐受性。保留率是近年来临床上评价癫痫患者长期治疗效果的新指标,综合反应了药物疗效、耐受性及适用性,同时包含了患者的个人意愿等,对抗癫痫治疗药物的选择具有实际的临床指导意义,已得到ILAE专家们的认可。目的:比较4种常用新型抗癫痫药(Antiepileptic drugs,AEDs)单药治疗新诊断癫痫患者的2年保留率,综合评估药物长期治疗性能,为癫痫患者的临床选药提供参考依据。方法:采用回顾性分析的方法,收集2007年1月-2016年10月在大连医科大学附属第一医院癫痫门诊就诊的癫痫患者临床资料,从中筛选出分别接受了托吡酯(topiramate,TPM)、拉莫三嗪(lamotrigine,LTG)、奥卡西平(oxcarbazepine,OXC)、左乙拉西坦(levetiracetam,LEV)正规单药治疗的新诊断癫痫患者共计376例,随访观察2年,记录治疗过程中的发作频率变化、不良反应、停药原因。分别在6个月、12个月和2年时计算4种新型AEDs单药治疗的保留率,保留率=随访时坚持初始单药治疗人数/起始该药治疗的总人数×100%;通过Kaplan-Meier生存分析法计算累计保留率。对保留达2年的患者,分别以有效率、年无发作率为指标评价临床疗效;分析比较各自停药原因。使用SPSS 17.0软件进行统计学处理。结果:1、符合纳入和排除标准的患者376例,TPM组134例,LTG组80例,OXC 组 79 例,LEV 组 83 例。女性 174 例(46.3%),男性 202 例(53.7%)。年龄1.5-86岁,平均年龄31.8±19.2岁。用药前病程4天-55年。原发性癫痫167例(44.4%),继发性癫痫209例(55.6%)。部分性发作248例(66.0%),全面性发作128例(34.0%)。Cox回归模型示性别、年龄、用药前病程、病因、发作类型不是影响保留率的潜在危险因素(P0.05)。2、保留率:6个月时,保留率为LTG组91.3%、TPM组82.1%、LEV组79.5%、OXC组78.5%,4组间比较差异无统计学意义(P0.05)。12个月时,保留率为LTG 组 81.3%、TPM 组 74.6%、LEV 组 66.3%、OXC 组 65.8%,4 组间比较差异无统计学意义(P0.05)。2年时,保留率依次为LTG组70.0%、LEV组63.9%、OXC组59.5%、TPM组58.2%,4组间比较无显著差异(P0.05)。观察结束时(2年),采用Kaplan-Meier生存分析法计算的累积保留率显示上述类似结果。3、临床疗效:2年时有效率依次为LTG组91.1%、LEV组90.6%、TPM组87.2%、OXC组85.1%,4组间比较无显著差异(P0.05)。2年时年无发作率依次为TPM组 61.5%、LEV 组 60.4%、LTG 组 57.1%、OXC 组38.3%,差异无统计学意义(p0.05)。4、导致停药的不良反应:TPM组最常见的为中枢神经系统问题,表现为记忆减退、反应迟钝,其次为泌尿系结石,其他少见为体重下降、皮疹。LTG组主要为肝功异常、皮疹。OXC组主要为皮疹,其次为中枢神经系统问题(困倦)。LEV组主要为精神行为异常,表现为易激惹、行为紊乱,其次为中枢神经系统问题,表现为困倦。5、停药原因:导致4组新型AEDs停药的首要原因均为无效,分别占停药原因的LTG组75.0%、LEV组70.0%、OXC组46.9%、TPM组44.6%,其中,LTG组与OXC组、TPM组比较差异有统计学意义(P0.05),LEV组与TPM组比较差异有统计学意义(P0.05),其他药物之间比较,差异无统计学意义(P0.05)。其次,停药原因为不良反应,分别占停药原因的TPM组32.1%、OXC组31.2%、LTG组20.8%、LEV组13.3%,4组间比较差异无统计学意义(P0.05)。其他停药原因包括依从性差、经济原因、联合应用其他抗癫痫药。6、2年时每种AEDs平均日剂量停药组高于保留组,差异均有统计学意义(P0.05)。结论:1、4种新型AEDs单药治疗的保留率在2年内均逐渐下降;LTG组在各阶段保留率最高,OXC组在6个月、12个月时保留率最低,TPM组在2年时保留率最低。2、4种新型AEDs单药治疗的临床疗效相当。3、导致4种新型AEDs停药的首要原因均为无效,其次为不良反应。
[Abstract]:BACKGROUND: Epilepsy is a common and frequently-occurring disease of the nervous system. Long-term drug therapy is currently recognized as the main measure. New antiepileptic drugs have been widely used in clinic because of their broad antiepileptic spectrum, good seizure control rate and less adverse reaction rate. Many studies have confirmed their effectiveness and tolerance. It is a new index for evaluating the long-term therapeutic effect of epilepsy patients in recent years. It comprehensively reflects the efficacy, tolerance and applicability of drugs, and also includes the individual wishes of patients. It has practical clinical significance for the selection of antiepileptic drugs and has been approved by ILAE experts. Objective: To compare four new antiepileptic drugs. The two-year retention rate of antiepileptic drugs (AEDs) in newly diagnosed epilepsy patients was evaluated comprehensively to provide reference for the clinical selection of epileptic patients. Clinical data of 376 newly diagnosed epilepsy patients who received topiramate (TPM), lamotrigine (LTG), oxcarbazepine (OXC) and levetiracetam (LEV) were selected. The frequency of seizures and adverse reactions during the treatment were recorded. Reasons for discontinuation were calculated at 6 months, 12 months, and 2 years, respectively. The retention rate = the number of patients who had adhered to the initial single-drug treatment at follow-up * 100%; the cumulative retention rate was calculated by Kaplan-Meier survival analysis. Results: 1. 376 patients, 134 patients in TPM group, 80 patients in LTG group, 79 patients in OXC group, 83 patients in LEV group, 174 women (46.3%) and 202 men (53.7%) met the inclusion and exclusion criteria. Cox regression model showed that sex, age, course of treatment, etiology, seizure type were not the potential risk factors affecting the retention rate (P 0.05). The retention rate was 91.3% in LTG group at 6 months. At 12 months, the retention rate was 81.3% in LTG group, 74.6% in TPM group, 66.3% in LEV group, 65.8% in OXC group. There was no significant difference among the four groups (P 0.05). At 2 years, the retention rate was 70.0% in LTG group, 63.9% in LEV group, 59.5% in OXC group, 58.2% in TPM group and 58.2% in OXC group. At the end of the observation (2 years), the cumulative retention rate calculated by Kaplan-Meier survival analysis showed the similar results. 3. Clinical efficacy: at 2 years, the effective rate was 91.1% in LTG group, 90.6% in LEV group, 87.2% in TPM group, 85.1% in OXC group, and there was no significant difference among the four groups (P 0.05). At 2 years, the annual no attack rate was 61.5% in TPM group and 61.5% in LEV group. 60.4%, LTG group 57.1%, OXC group 38.3%, the difference was not statistically significant (p0.05). 4, resulting in withdrawal of adverse reactions: TPM group the most common central nervous system problems, for memory loss, slow response, followed by urinary calculi, other rare for weight loss, rash. LTG group mainly for liver dysfunction, rash. OXC group mainly for rash, its most common rash. Secondly, the central nervous system problems (drowsiness). LEV group mainly for mental behavior disorders, irritability, behavior disorders, followed by the central nervous system problems, performance drowsiness. 5. Drug withdrawal reasons: leading to the four groups of new AEDs withdrawal of the primary causes were ineffective, accounting for 75.0% of the LTG group, 70.0% of LEV group, 46.9% of OXC group, 44.6% of TPM group, respectively. There was significant difference between LTG group and OXC group, TPM group (P 0.05), LEV group and TPM group (P 0.05), and there was no significant difference between other drugs (P 0.05). Secondly, the reasons for drug withdrawal were adverse reactions, which accounted for 32.1% of TPM group, 31.2% of OXC group, 20.8% of LTG group, 13.3% of LEV group. There was no significant difference between the two groups (P 0.05). Other reasons for withdrawal included poor compliance, economic reasons, combined use of other antiepileptic drugs. Retention rate was the highest in OXC group at 6 months and the lowest at 12 months. Retention rate was the lowest in TPM group at 2 years. The clinical efficacy of four new AEDs monotherapy was similar. 3. The primary cause of discontinuation of four new AEDs was ineffective, followed by adverse reactions.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R742.1
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本文编号：2181019