背景:尽管大多数癫痫患者完全停止癫痫发作,尽管使用抗癫痫药物(ASM)作为单一疗法或综合疗法,但仍有约三分之一的患者继续癫痫发作.在这次审查中,我们总结了随机对照试验(RCTs)中关于西诺比特作为一种或多种伴随ASM未控制的局灶性癫痫的附加治疗的证据。
目的:为了评估西诺比特口服治疗耐药局灶性发作性癫痫的疗效和耐受性,
方法:我们检索了Cochrane研究注册(CRSWeb)和MEDLINEOvid(2022年9月)。此外,我们联系了cenobamate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。
方法:RCTs比较了在一个或多个伴随ASM未控制的局灶性癫痫患者中添加西尼obamate与安慰剂或其他ASM。
方法:两个综述作者独立选择了纳入的试验,提取的数据,执行偏差风险评估,并使用等级方法评估证据的确定性。我们的主要结果是总癫痫发作频率至少减少50%,癫痫发作自由,以及不良事件的发生。我们在主要分析中使用了意向治疗方法。对于每个结果,我们使用其95%置信区间(CI)估计了汇总风险比(RR)。我们在结果摘要表中总结了每个结果的影响和证据的确定性的估计。
结果:我们纳入了两项研究(659名成年参与者,442分配给西诺本和217分配给安慰剂)。与安慰剂相比,任何剂量的西诺膦酸盐的癫痫发作频率至少降低50%的总RR为2.17(52%对24%,95%CI1.66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,任何剂量的附加西伯酸盐的癫痫发作自由RR为4.45(16%对5%,95%CI2.25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,任何剂量的西伯那酯的不良事件发生的RR为1.14(77%对67%,95%CI1.02至1.27;2项研究,659名参与者;中度确定性证据)。我们判断这两个纳入的RCT存在低或不清楚的偏倚风险。两项研究都是由生产cenobamate的制药公司赞助的。
结论:在由一个或多个伴随ASM控制的局灶性癫痫的成人中,添加西诺比特可能比安慰剂更好地将癫痫发作频率降低至少50%,并实现癫痫发作自由(中度确定性)。它的使用可能与不良事件的风险增加有关(中度确定性)。进一步的前瞻性,与其他ASM相比,需要进行对照试验来评估附加西诺比特的疗效和耐受性。西诺比特作为儿童局灶性癫痫辅助治疗的疗效和耐受性需要进一步研究。最后,在患有其他癫痫类型(例如,全身性癫痫)或特定癫痫综合征的人中,添加西伯酸盐治疗的长期疗效和耐受性,以及它作为单一疗法的用途,需要额外的研究。
BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: 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 In addition, we contacted the manufacturer of cenobamate and experts in the field to enquire after any ongoing or unpublished studies.
METHODS: RCTs comparing add-on cenobamate to placebo or another ASM in people with focal epilepsy uncontrolled by one or more concomitant ASMs.
METHODS: 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.
RESULTS: 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.
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.