五种广谱抗癫痫药物辅助治疗难治性癫痫的疗效和安全性:系统综述和网络荟萃分析。

IF 7.4 2区 医学 Q1 CLINICAL NEUROLOGY
CNS drugs Pub Date : 2023-10-01 Epub Date: 2023-08-17 DOI:10.1007/s40263-023-01029-0
Hecheng Wang, Haoran Wang, Yi Liu, Jing Zhao, Xuewen Niu, Lei Zhu, Xiaomin Ma, Yu Zong, Yinglin Huang, Wei Zhang, Yanshuo Han
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引用次数: 0

摘要

背景:总体而言,多达三分之一的癫痫患者患有耐药性癫痫。然而,以前没有荟萃分析支持广谱抗癫痫药物选择辅助治疗难治性癫痫的指南。在本荟萃分析中,我们评估了三种第二代广谱抗癫痫药物拉莫三嗪(LTG)、左乙拉西坦(LEV)和托吡酯(TPM),以及两种第三代广谱抗痫药物帕帕奈(PER)和拉沙酰胺(LCM)辅助治疗难治性癫痫的疗效和安全性。方法:从成立到2022年7月15日,我们系统地搜索了PubMed、Embase和CENTRAL。纳入荟萃分析的研究需要满足以下标准:(1)为随机、双盲临床试验;(2) 包括临床诊断为耐药癫痫的年龄>2岁的患者;(3) 除滴定阶段外,治疗期至少为8周;和(4)报告癫痫反应的结果、癫痫自由度和因治疗引起的不良反应而退出的比率。提取数据,由两位作者使用RoB2工具独立评估每项研究的偏倚风险。我们通过Stata的mvmeta和网络包中的一组程序对每个结果进行了网络荟萃分析。计算95%置信区间的相对优势比作为分析结果。累积排序曲线下的表面(SUCRA)和平均排序用于对这些处理进行排序。结果:42项随机对照试验(RCT)(LTG安慰剂:n=6,LEV安慰剂:n=13,TPM安慰剂:n=9,PER安慰剂:n=6,LCM安慰剂:n=7,LEV-TPM:n=1)包括10257名参与者(LTG=569,LEV=1626,TPM=701,PER=1734,LCM=1908,安慰剂=3719)。左乙拉西坦在将癫痫发作频率降低50%至TPM方面具有亚同等疗效[比值比(OR)1.00、95%置信区间(CI)0.73-1.38],与LCM(OR 1.49,95%CI 1.11-2.01)和PER(OR 1.68,95%CI 1.24-2.29)相比,LEV的癫痫发作频率降低率≥50%。与TPM(OR 1.87,95%CI 1.20-2.89)、PER(OR2.23,95%CI 1.12-4.43)和LCM(OR2.97,95%CI 1.46-6.05)相比,左乙拉西坦与癫痫发作自由参与者的比例也更高。此外,与PER(OR 0.63,95%CI 0.46-0.85)和TPM(OR 0.51,95%CI 0.36-0.72与几种第二代药物(LEV和LTG)相比,辅助治疗难治性癫痫在疗效和安全性方面具有优势。左乙拉西坦是辅助治疗难治性癫痫的首选药物。Perampanel和LCM在这五种药物中的疗效和安全性方面没有优势。注册:PROSPERO注册号CRD42022344153;最后一次编辑于2022年12月23日。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Efficacy and Safety of Five Broad-Spectrum Antiseizure Medications for Adjunctive Treatment of Refractory Epilepsy: A Systematic Review and Network Meta-analysis.

Efficacy and Safety of Five Broad-Spectrum Antiseizure Medications for Adjunctive Treatment of Refractory Epilepsy: A Systematic Review and Network Meta-analysis.

Background: Overall, up to one-third of epilepsy patients have drug-resistant epilepsy. However, there was previously no meta-analysis to support the guidelines for broad-spectrum antiseizure medication selection for the adjunctive treatment of refractory epilepsy. In the present meta-analysis, we assessed the efficacy and safety of three second-generation broad-spectrum antiseizure medications, lamotrigine (LTG), levetiracetam (LEV), and topiramate (TPM), and two third-generation broad-spectrum antiseizure medications, perampanel (PER) and lacosamide (LCM), for the adjunctive treatment of refractory epilepsy.

Methods: We systematically searched PubMed, Embase, and CENTRAL from inception to July 15, 2022. The studies included in the meta-analysis were required to meet the following criteria: (1) be randomized, double-blind clinical trials; (2) include patients aged >2 years with a clinical diagnosis of drug-resistant epilepsy; (3) have at least 8 weeks for the treatment period excluding the titration phase; and (4) report the outcomes of seizure response, seizure freedom and the withdrawal rate due to treatment-emergent adverse effects. Data were extracted, and the risk of bias for each study was assessed by two authors independently using RoB2 tools. We performed the network meta-analysis for each outcome through a group of programs in the mvmeta and network packages in Stata. Relative odds ratios with 95% confidence intervals were calculated as the result of the analyses. The surface under the cumulative ranking curve (SUCRA) and mean ranks were used to rank these treatments.

Results: Forty-two randomized controlled trials (RCTs) (LTG-placebo: n = 6, LEV-placebo: n = 13, TPM-placebo: n = 9, PER-placebo: n = 6, LCM-placebo: n = 7, LEV-TPM: n = 1) with 10257 participants (LTG = 569, LEV = 1626, TPM = 701, PER = 1734, LCM = 1908, placebo = 3719) were included. Levetiracetam had subequal efficacy in 50 % seizure frequency reduction to TPM [odds ratio (OR) 1.00, 95% confidence interval (CI) 0.73-1.38], and LEV had a higher rate of ≥ 50% seizure frequency reduction than LCM (OR 1.49, 95% CI 1.11-2.01) and PER (OR 1.68, 95% CI 1.24-2.29). Levetiracetam was also related to a higher proportion of seizure freedom participants than TPM (OR 1.87, 95% CI 1.20-2.89), PER (OR 2.23, 95% CI 1.12-4.43), and LCM (OR 2.97, 95% CI 1.46-6.05). In addition, LEV was associated with a lower risk of experiencing at least one treatment-emergent adverse event (TEAE) than PER (OR 0.63, 95% CI 0.46-0.85) and TPM (OR 0.51, 95 % CI 0.36-0.72) and a lower proportion of patients experiencing TEAEs leading to discontinuation than PER (OR 0.51, 95% CI 0.27-0.97) and TPM (OR 0.50, 95 % CI 0.27-0.93).

Conclusions: Third-generation drugs (PER and LCM) had no advantages in terms of efficacy and safety for adjunctive treatment of refractory epilepsy compared with several second-generation drugs (LEV and LTG). Levetiracetam was the priority choice for adjunctive treatment of refractory epilepsy. Perampanel and LCM had no advantages in terms of efficacy and safety among the five drugs.

Registration: PROSPERO registration number, CRD42022344153; last edited on December 23, 2022.

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来源期刊
CNS drugs
CNS drugs 医学-精神病学
CiteScore
12.00
自引率
3.30%
发文量
82
审稿时长
6-12 weeks
期刊介绍: CNS Drugs promotes rational pharmacotherapy within the disciplines of clinical psychiatry and neurology. The Journal includes: - Overviews of contentious or emerging issues. - Comprehensive narrative reviews that provide an authoritative source of information on pharmacological approaches to managing neurological and psychiatric illnesses. - Systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. - Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in neurology and psychiatry. - Original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in CNS Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.
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