NIHR University College London Hospitals Biomedical Research Centre, UCL Queen Square Institute of Neurology, London, UK.
Chalfont Centre for Epilepsy, Chalfont St. Peter, UK.
Epilepsia. 2022 Jan;63(1):139-149. doi: 10.1111/epi.17134. Epub 2021 Nov 23.
We determined retention on open-label cenobamate therapy in the clinical development program to assess the long-term efficacy and tolerability of adjunctive cenobamate in individuals with uncontrolled focal seizures.
Data from two randomized, controlled cenobamate studies and one open-label safety and pharmacokinetic study were pooled. Based on the percentage of participants remaining on treatment, retention rates were estimated using Kaplan-Meier survival analyses. We performed two additional analyses to assess factors contributing to retention, stratifying a robust data set (through 2 years) by cenobamate modal dose and frequently used concomitant anti-seizure medications. Cenobamate discontinuations and treatment-emergent adverse events were summarized.
Data from 1844 participants were pooled: 149 from a single-dose randomized trial, 355 from a multi-dose randomized trial, and 1340 from an open-label safety and pharmacokinetic study. Most participants from randomized trials continued in open-label extensions, and pooled data represent >95% of participants exposed to cenobamate. Baseline characteristics and disease and treatment histories were similar across studies. Median duration of cenobamate exposure was 34 months, with a median modal dose of 200 mg/day. Kaplan-Meier estimates of cumulative cenobamate retention rates were 80% at 1 year and 72% at 2 years. Once participants reached the maintenance phase, retention rates were consistently high in participants receiving ≥100 mg/day cenobamate, and concomitant anti-seizure medications did not affect long-term retention. By 2 years, 535 (29%) had actually discontinued cenobamate; the most common reasons for discontinuation were adverse events (37.6%), withdrawal of consent (21.1%), and other (16.8%).
Treatment retention rates provide a proxy measure for long-term efficacy, safety, tolerability, and adherence. The consistently high retention rates we found suggest that cenobamate may be an effective and well-tolerated new treatment option for people with drug-resistant focal seizures.
我们确定了开放性依诺加巴治疗的保留率，以评估辅助依诺加巴在未控制局灶性发作患者中的长期疗效和耐受性。
汇总了两项随机对照依诺加巴研究和一项开放性安全性和药代动力学研究的数据。根据仍在接受治疗的参与者的百分比，使用 Kaplan-Meier 生存分析估计保留率。我们进行了另外两项分析，以评估与保留率相关的因素，通过依诺加巴的模式剂量和常用伴随抗癫痫药物对稳健数据集（2 年）进行分层。总结了依诺加巴停药和治疗中出现的不良事件。
汇总了 1844 名参与者的数据：来自单剂量随机试验的 149 名，多剂量随机试验的 355 名，开放性安全性和药代动力学研究的 1340 名。大多数来自随机试验的参与者继续参加开放性扩展研究，汇总数据代表暴露于依诺加巴的参与者超过 95%。研究之间的基线特征、疾病和治疗史相似。依诺加巴暴露的中位持续时间为 34 个月，中位模式剂量为 200mg/天。依诺加巴累积保留率的 Kaplan-Meier 估计值在 1 年时为 80%，在 2 年时为 72%。一旦参与者达到维持阶段，每天接受≥100mg 依诺加巴治疗的参与者的保留率始终较高，伴随的抗癫痫药物不会影响长期保留率。2 年内，535 名（29%）实际上停止了依诺加巴治疗；停药的最常见原因是不良事件（37.6%）、同意撤销（21.1%）和其他原因（16.8%）。
治疗保留率提供了长期疗效、安全性、耐受性和依从性的替代衡量标准。我们发现的保留率始终很高，表明依诺加巴可能是一种有效且耐受性良好的新治疗选择，适用于耐药性局灶性发作的患者。
