Innovation, Research and Teaching Service (SABES-ASDAA), Teaching Hospital of the Paracelsus Medical Private University (PMU), Bolzano, Italy.
Neurological Clinic, Marche Polytechnic University, Ancona, Italy.
Cochrane Database Syst Rev. 2024 Aug 1;8(8):CD014941. doi: 10.1002/14651858.CD014941.pub2.
Although most people with epilepsy achieve complete seizure cessation, approximately one-third of those with the condition continue experiencing seizures despite the use of antiseizure medications (ASMs) given as monotherapy or polytherapy. In this review, we summarised the evidence from randomised controlled trials (RCTs) about cenobamate as an add-on treatment for focal epilepsy uncontrolled by one or more concomitant ASMs.
To assess the efficacy and tolerability of add-on oral cenobamate for the treatment of drug-resistant focal-onset seizures, defined as seizures persisting despite treatment with one or more ASMs.
We searched the Cochrane Register of Studies (CRS Web) and MEDLINE Ovid (September 2022). In addition, we contacted the manufacturer of cenobamate and experts in the field to enquire after any ongoing or unpublished studies.
RCTs comparing add-on cenobamate to placebo or another ASM in people with focal epilepsy uncontrolled by one or more concomitant ASMs.
Two review authors independently selected trials for inclusion, extracted data, performed risk of bias assessment, and assessed the certainty of the evidence using the GRADE approach. Our primary outcomes were at least a 50% reduction in total seizure frequency, seizure freedom, and the occurrence of adverse events. We used an intention-to-treat approach for our primary analyses. For each outcome we estimated summary risk ratios (RRs) with their 95% confidence intervals (CIs). We summarised the estimates of effects and certainty of the evidence for each outcome in a summary of findings table.
We included two studies (659 adult participants, 442 allocated to cenobamate and 217 to placebo). The overall RR for at least a 50% reduction in seizure frequency for add-on cenobamate at any dose compared to placebo was 2.17 (52% versus 24%, 95% CI 1.66 to 2.84; 2 studies, 605 participants; moderate-certainty evidence). The RR for seizure freedom for add-on cenobamate at any dose compared to placebo was 4.45 (16% versus 5%, 95% CI 2.25 to 8.78; 2 studies, 605 participants; moderate-certainty evidence). The RR for the occurrence of adverse events for add-on cenobamate at any dose compared to placebo was 1.14 (77% versus 67%, 95% CI 1.02 to 1.27; 2 studies, 659 participants; moderate-certainty evidence). We judged the two included RCTs as at low or unclear risk of bias. Both studies were sponsored by the drug company that produces cenobamate.
AUTHORS' CONCLUSIONS: Add-on cenobamate is probably better than placebo in reducing the frequency of seizures by at least 50% and in achieving seizure freedom in adults with focal epilepsy uncontrolled by one or more concomitant ASMs (moderate level of certainty). Its use is probably associated with an increased risk of adverse events (moderate level of certainty). Further prospective, controlled trials are required to evaluate the efficacy and tolerability of add-on cenobamate compared to other ASMs. The efficacy and tolerability of cenobamate as adjunctive treatment for focal epilepsy in children should be further investigated. Finally, the long-term efficacy and tolerability of add-on cenobamate treatment in people with other epilepsy types (e.g. generalised epilepsy) or specific epilepsy syndromes, as well as its use as monotherapy, require additional study.
尽管大多数癫痫患者能够完全停止发作，但大约三分之一的患者尽管使用了单药或多药抗癫痫药物（ASM）治疗，仍继续出现发作。在本综述中，我们总结了随机对照试验（RCT）的证据，评估了作为附加治疗药物，加巴喷丁在一种或多种伴随 ASM 治疗下仍无法控制的局灶性癫痫中的疗效和耐受性。
评估口服加巴喷丁作为附加治疗药物治疗药物难治性局灶性发作的疗效和耐受性，定义为尽管使用一种或多种 ASM 治疗仍持续发作的发作。
我们检索了 Cochrane 对照试验注册库（CRS Web）和 MEDLINE Ovid（2022 年 9 月）。此外，我们联系了加巴喷丁的制造商和该领域的专家，询问任何正在进行或未发表的研究。
比较加巴喷丁作为附加治疗药物与安慰剂或另一种 ASM 治疗一种或多种伴随 ASM 治疗仍无法控制的局灶性癫痫的 RCT。
两位综述作者独立选择纳入的试验，提取数据，进行风险偏倚评估，并使用 GRADE 方法评估证据的确定性。我们的主要结局是至少 50%减少总发作频率、无发作和不良事件的发生。我们对主要分析采用意向治疗方法。对于每个结局，我们估计了摘要风险比（RR）及其 95%置信区间（CI）。我们在一个发现总结表中总结了每个结局的效应估计值和证据确定性。
我们纳入了两项研究（659 名成年参与者，442 名分配到加巴喷丁组，217 名分配到安慰剂组）。与安慰剂相比，任何剂量的加巴喷丁作为附加治疗药物，至少减少 50%发作频率的总体 RR 为 2.17（52%对 24%，95%CI 1.66 至 2.84；2 项研究，605 名参与者；中等确定性证据）。与安慰剂相比，任何剂量的加巴喷丁作为附加治疗药物，达到无发作的 RR 为 4.45（16%对 5%，95%CI 2.25 至 8.78；2 项研究，605 名参与者；中等确定性证据）。与安慰剂相比，任何剂量的加巴喷丁作为附加治疗药物，发生不良事件的 RR 为 1.14（77%对 67%，95%CI 1.02 至 1.27；2 项研究，659 名参与者；中等确定性证据）。我们判断纳入的两项 RCT 为低风险或不确定风险的偏倚。这两项研究均由生产加巴喷丁的药物公司赞助。
在一种或多种伴随 ASM 治疗仍无法控制的局灶性癫痫成人中，加巴喷丁作为附加治疗药物可能比安慰剂更能有效减少至少 50%的发作频率和实现无发作（中等确定性）。它的使用可能与不良事件的风险增加有关（中等确定性）。需要进一步开展前瞻性、对照试验来评估加巴喷丁与其他 ASM 相比的疗效和耐受性。加巴喷丁作为附加治疗药物治疗儿童局灶性癫痫的疗效和耐受性需要进一步研究。最后，加巴喷丁作为附加治疗药物在其他类型癫痫（如全面性癫痫）或特定癫痫综合征中的疗效和耐受性，以及其作为单药治疗的使用，需要进一步研究。
