Liverpool Reviews and Implementation Group, Institute of Population Health, University of Liverpool, Liverpool, UK.
Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Cochrane Database Syst Rev. 2022 Mar 14;3(3):CD011501. doi: 10.1002/14651858.CD011501.pub3.
This is an updated version of the Cochrane Review previously published in 2019. Epilepsy is one of the most common neurological disorders. It is estimated that up to 30% of individuals with epilepsy continue to have epileptic seizures despite treatment with an antiepileptic drug. These patients are classified as drug-resistant and require treatment with a combination of multiple antiepileptic drugs. Brivaracetam is a third-generation antiepileptic drug that is a high-affinity ligand for synaptic vesicle protein 2A. In this review we investigated the use of brivaracetam as add-on therapy for epilepsy.
To evaluate the efficacy and tolerability of brivaracetam when used as add-on treatment for people with drug-resistant epilepsy.
For the latest update we searched the following databases on 7 September 2021: the Cochrane Register of Studies (CRS Web); MEDLINE (Ovid) 1946 to 3 September 2021. CRS Web includes randomised controlled trials (RCTs) and quasi-RCTs from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy.
We searched for parallel-group RCTs that recruited people of any age with drug-resistant epilepsy. We accepted studies with any level of blinding (double-blind, single-blind, or unblinded).
In accordance with standard Cochrane methodological procedures, two review authors independently assessed trials for inclusion before evaluating trial quality and extracting relevant data. The primary outcome to be assessed was 50% or greater reduction in seizure frequency. Secondary outcomes were: seizure freedom, treatment withdrawal for any reason, treatment withdrawal due to adverse events, the proportion of participants who experienced any adverse events, and drug interactions. We used an intention-to-treat population for all primary analyses, and presented results as risk ratios (RRs) with 95% confidence intervals (CIs).
We did not identify any new studies for this update, therefore the results and conclusions of the review are unchanged. The previous review included six studies involving a total of 2411 participants. Only one study included participants with both focal and generalised onset seizures; the other five trials included participants with focal onset seizures only. Study participants were aged 16 to 80 years. Treatment periods ranged from 7 to 16 weeks. We judged two studies to have low risk of bias and four to have unclear risk of bias. Details on the method used for allocation concealment and how blinding was maintained were insufficient in one study each. One study did not report all outcomes prespecified in the trial protocol, and there were discrepancies in reporting in a further study. Participants receiving brivaracetam add-on were more likely to experience a 50% or greater reduction in seizure frequency than those receiving placebo (RR 1.81, 95% CI 1.53 to 2.14; 6 studies; moderate-certainty evidence). Participants receiving brivaracetam were more likely to attain seizure freedom; however, the evidence is of low certainty (RR 5.89, 95% CI 2.30 to 15.13; 6 studies). The incidence of treatment withdrawal for any reason was slightly greater for participants receiving brivaracetam compared to those receiving placebo (RR 1.27, 95% CI 0.94 to 1.74; 6 studies; low-certainty evidence). The risk of participants experiencing one or more adverse events did not differ significantly following treatment with brivaracetam compared to placebo (RR 1.08, 95% CI 1.00 to 1.17; 5 studies; moderate-certainty evidence). However, participants receiving brivaracetam did appear to be more likely to withdraw from treatment due to adverse events compared with those receiving placebo (RR 1.54, 95% CI 1.02 to 2.33; 6 studies; low-certainty evidence).
AUTHORS' CONCLUSIONS: When used as add-on therapy for individuals with drug-resistant epilepsy, brivaracetam may be effective in reducing seizure frequency and may aid patients in achieving seizure freedom. However, add-on brivaracetam is probably associated with a greater proportion of treatment withdrawals due to adverse events compared with placebo. It is important to note that only one of the eligible studies included participants with generalised epilepsy. None of the included studies involved participants under the age of 16, and all studies were of short duration. Consequently, the findings of this review are mainly applicable to adult patients with drug-resistant focal epilepsy. Future research should focus on investigating the tolerability and efficacy of brivaracetam during longer-term follow-up, as well as assess the efficacy and tolerability of add-on brivaracetam in managing other types of seizures and in other age groups.
这是 Cochrane 综述的更新版本，先前于 2019 年发表。癫痫是最常见的神经障碍之一。据估计，多达 30%的癫痫患者尽管接受了抗癫痫药物治疗，但仍有癫痫发作。这些患者被归类为耐药性，需要使用多种抗癫痫药物联合治疗。布瓦卡坦是一种第三代抗癫痫药物，是突触囊泡蛋白 2A 的高亲和力配体。在本综述中，我们研究了布瓦卡坦作为附加治疗药物用于耐药性癫痫的效果和耐受性。
评估布瓦卡坦作为附加治疗药物用于耐药性癫痫患者的疗效和耐受性。
截至 2021 年 9 月 7 日，我们对以下数据库进行了最新更新：Cochrane 研究注册库（CRS Web）；MEDLINE（Ovid）1946 年至 2021 年 9 月 3 日。CRS Web 包括来自 PubMed、Embase、ClinicalTrials.gov、世界卫生组织国际临床试验注册平台、Cochrane 中央对照试验注册库（CENTRAL）和包括 Cochrane 癫痫组在内的专门注册库的随机对照试验（RCT）和准 RCT。
我们检索了招募任何年龄耐药性癫痫患者的平行组 RCT。我们接受了任何水平的盲法（双盲、单盲或非盲）的研究。
根据标准的 Cochrane 方法学程序，两名综述作者独立评估试验纳入情况，然后评估试验质量并提取相关数据。主要结局是 50%或更大的癫痫发作频率降低。次要结局是：无癫痫发作、因任何原因停药、因不良事件停药、发生任何不良事件的参与者比例，以及药物相互作用。我们对所有主要分析均采用意向治疗人群，结果以风险比（RR）及其 95%置信区间（CI）表示。
我们没有发现任何新的研究，因此综述的结果和结论保持不变。之前的综述纳入了六项涉及 2411 名参与者的研究。只有一项研究纳入了既有局灶性又有全面性发作的患者；其余五项试验仅纳入了局灶性发作的患者。研究参与者年龄在 16 至 80 岁之间。治疗期从 7 至 16 周不等。我们判断两项研究的偏倚风险低，四项研究的偏倚风险不确定。每项研究的分配隐藏方法和如何维持盲法的细节都不够详细。一项研究未报告试验方案中所有预定的结局，另一项研究的报告结果存在差异。接受布瓦卡坦附加治疗的患者比接受安慰剂的患者更有可能出现 50%或更大的癫痫发作频率降低（RR 1.81，95%CI 1.53 至 2.14；6 项研究；中等确定性证据）。接受布瓦卡坦治疗的患者更有可能达到无癫痫发作，但证据质量低（RR 5.89，95%CI 2.30 至 15.13；6 项研究）。因任何原因停药的发生率，接受布瓦卡坦治疗的患者略高于接受安慰剂的患者（RR 1.27，95%CI 0.94 至 1.74；6 项研究；低确定性证据）。与安慰剂相比，接受布瓦卡坦治疗的患者出现一种或多种不良事件的风险没有显著差异（RR 1.08，95%CI 1.00 至 1.17；5 项研究；中等确定性证据）。然而，与接受安慰剂的患者相比，接受布瓦卡坦治疗的患者因不良事件而退出治疗的可能性似乎更高（RR 1.54，95%CI 1.02 至 2.33；6 项研究；低确定性证据）。
当作为耐药性癫痫患者的附加治疗药物时，布瓦卡坦可能有助于降低癫痫发作频率，并帮助患者实现无癫痫发作。然而，与安慰剂相比，添加布瓦卡坦可能与更多的因不良事件而停药相关。重要的是，纳入的研究中只有一项研究包括了全面性癫痫患者。没有一项研究涉及 16 岁以下的参与者，所有研究的持续时间都很短。因此，本综述的结果主要适用于耐药性局灶性癫痫的成年患者。未来的研究应侧重于调查布瓦卡坦在更长时间的随访中的耐受性和疗效，以及评估布瓦卡坦附加治疗在管理其他类型的癫痫发作和其他年龄组中的疗效和耐受性。
