Vossler David G, Rosenfeld William E, Stern Sean, Wade Clarence T, Ferrari Louis, Kerr Wesley T, Wechsler Robert
University of Washington School of Medicine, Seattle, Washington, USA.
Comprehensive Epilepsy Care Center for Children and Adults, St. Louis, Missouri, USA.
Epilepsia. 2023 Oct;64(10):2644-2652. doi: 10.1111/epi.17724. Epub 2023 Aug 7.
In this post hoc analysis of a subset of patients from a long-term, open-label phase 3 study, we assessed ≥50%, ≥75%, ≥90%, and 100% seizure reduction and sustainability of these responses with cenobamate using a time-to-event analytical approach.
Of 240 patients with uncontrolled focal seizures who had adequate seizure data available, 214 completed the 12-week titration phase and received ≥1 dose of cenobamate in the maintenance phase (max dose 400 mg/day) and were included in this post hoc analysis. Among patients who met an initial given seizure-reduction level (≥50%, ≥75%, ≥90%, or 100%), sustainability of that response was measured using a time-to-event methodology. An event was defined as the occurrence of a study visit at which the seizure frequency during the interval since the prior study visit exceeded the initially attained reduction level. Study visits during the maintenance phase occurred at 3-month intervals.
Of the 214 patients analyzed, 188 (88%), 177 (83%), 160 (75%), and 145 (68%) met ≥50%, ≥75%, ≥90%, and 100% seizure-reduction responses, respectively, for at least one study visit interval during the maintenance phase. The median (95% confidence interval [CI]) time to first visit without a ≥50% seizure reduction was not reached by 30 months of follow-up (53% of patients maintained their initial ≥50% seizure reduction). Median (95% CI) time to first visit without sustaining the initial ≥75%, ≥90%, or 100% seizure reduction was 13.0 (7.5-21.9) months, 7.5 (5.4-11.6) months, and 7.0 (5.3-10.4) months, respectively. Among the 145 patients who had 100% seizure reduction during at least one study visit, 22% remained seizure-free for at least 30 months and 63% had ≤3 study visits with seizures.
Adjunctive treatment with cenobamate led to sustained seizure reductions during the maintenance phase of the phase 3 safety study.
在一项针对长期开放标签3期研究中部分患者的事后分析中，我们采用事件发生时间分析方法，评估了使用司替戊醇使癫痫发作减少≥50%、≥75%、≥90%和100%的情况以及这些反应的可持续性。
在240例局灶性癫痫控制不佳且有足够癫痫发作数据的患者中，214例完成了12周的滴定阶段，并在维持阶段接受了≥1剂司替戊醇（最大剂量400mg/天），并纳入此次事后分析。在达到初始给定癫痫发作减少水平（≥50%、≥75%、≥90%或100%）的患者中，使用事件发生时间方法测量该反应的可持续性。事件定义为自上次研究访视以来的间隔期间癫痫发作频率超过最初达到的减少水平的研究访视的发生。维持阶段的研究访视每3个月进行一次。
在分析的214例患者中，分别有188例（88%）、177例（83%）、160例（75%）和145例（68%）在维持阶段的至少一个研究访视间隔中达到了癫痫发作减少≥50%、≥75%、≥90%和100%的反应。随访30个月时未达到首次访视时癫痫发作减少未≥50%的中位（95%置信区间[CI]）时间（53%的患者维持了最初≥50%的癫痫发作减少）。首次访视时未维持最初≥75%、≥90%或100%癫痫发作减少的中位（95%CI）时间分别为13.0（7.5 - 21.9）个月、7.5（5.4 - 11.6）个月和7.0（5.3 - 10.4）个月。在至少一次研究访视期间癫痫发作减少100%的145例患者中，22%至少30个月无癫痫发作，63%癫痫发作的研究访视≤3次。
在3期安全性研究的维持阶段，司替戊醇辅助治疗导致癫痫发作持续减少。
