Wheless James, Wechsler Robert T, Penovich Patricia, Segal Eric, Chez Michael, Coppola Antonietta, Datta Anita, D'Souza Wendyl, Najm Imad, Cappucci Sheri, Sainz-Fuertes Ricardo, Villanueva Vicente
University of Tennessee Health Science Center, Le Bonheur Children's Hospital, Memphis, TN, USA.
Idaho Comprehensive Epilepsy Center, Boise, ID, USA.
Epilepsy Behav. 2023 Oct;147:109369. doi: 10.1016/j.yebeh.2023.109369. Epub 2023 Aug 22.
To assess the effectiveness and safety/tolerability of perampanel (PER) in people with epilepsy (PWE) treated in everyday clinical practice for focal and generalized seizures, both in the total cohort and by age group.
The PERMIT Extension study was a pooled analysis of data from PWE included in two large previous clinical practice studies (PERMIT and PROVE). Retention was assessed over 12 months. Effectiveness was assessed based on total seizures and by seizure type (focal and generalized) after 3, 6, and 12 months of PER treatment and at final follow-up (last observation carried forward; "last visit"); assessments included responder rate (≥50% seizure frequency reduction from baseline) and seizure freedom rate (no seizures since at least the previous visit). Safety/tolerability was assessed throughout PER treatment by evaluating adverse events (AEs). All assessments were conducted for the total population and by age category (<12, ≥12 to <18, ≥18 to <65, and ≥65 years at baseline).
Full Analysis Set included 6,822 PWE (51.1% female; mean age, 36.9 years; mean duration of epilepsy 21.4 years) with 6,433, 4,648, and 6,233 PWE assessed for retention, effectiveness, and safety/tolerability, respectively. The majority of PWE (81.1%) were aged 18-64 at baseline, with 4.5% aged <12 years, 8.4% aged 12-17 years, and 5.9% aged ≥65 years. In the overall population, retention rates at 3, 6, and 12 months were 88.0%, 77.6%, and 61.4%, respectively; responder rates at 12 months were 58.5% for total seizures, 54.6% for focal seizures, and 77.7% for generalized seizures, and corresponding seizure freedom rates were 23.6%, 19.0%, and 51.3%, respectively. PER was effective regardless of age category, although effectiveness was greatest in PWE aged ≥65 years, for both focal and generalized seizures. In the overall population, the incidence of AEs was 49.2% and the most frequent AEs (≥5% of PWE) were dizziness/vertigo (13.4%), somnolence (8.8%), irritability (7.3%), and behavioral disorders (5.3%); AEs led to treatment discontinuation in 18.3% of PWE over 12 months. The incidence of AEs and the discontinuation rate due to AEs increased with increasing age (55.0% and 23.9%, respectively, in PWE aged ≥65 years).
In this study, the largest pooled analysis of PER clinical practice data conducted to date, PER was shown to be effective and generally well tolerated when used to treat people with focal or generalized epilepsy in everyday clinical practice, regardless of age category. No new or unexpected side effects emerged following long-term use in the real-world setting.
评估吡仑帕奈（PER）在日常临床实践中治疗局灶性和全身性癫痫患者（PWE）的有效性及安全性/耐受性，评估对象包括整个队列以及不同年龄组。
PERMIT扩展研究是对之前两项大型临床实践研究（PERMIT和PROVE）中纳入的PWE数据进行的汇总分析。随访12个月评估留存率。在PER治疗3、6和12个月以及最终随访（末次观察结转；“末次访视”）时，根据总发作次数和发作类型（局灶性和全身性）评估有效性；评估指标包括缓解率（发作频率较基线降低≥50%）和无发作率（自至少前一次访视起无发作）。在整个PER治疗期间，通过评估不良事件（AE）来评估安全性/耐受性。对总体人群以及按年龄类别（基线时<12岁、≥12至<18岁、≥18至<65岁和≥65岁）进行所有评估。
全分析集包括6822例PWE（51.1%为女性；平均年龄36.9岁；癫痫平均病程21.4年），分别有6433例、4648例和6233例PWE接受了留存率、有效性和安全性/耐受性评估。大多数PWE（81.1%）基线时年龄为18 - 64岁，4.5%年龄<12岁，8.4%年龄为12 - 17岁，5.9%年龄≥65岁。在总体人群中，3个月、6个月和12个月时的留存率分别为88.0%、77.6%和61.4%；12个月时总发作的缓解率为58.5%，局灶性发作的缓解率为54.6%，全身性发作的缓解率为77.7%，相应的无发作率分别为23.6%、19.0%和51.3%。无论年龄类别如何，PER均有效，尽管对于局灶性和全身性发作，≥65岁的PWE有效性最高。在总体人群中，AE的发生率为49.2%，最常见的AE（≥5%的PWE）为头晕/眩晕（13.4%）、嗜睡（8.8%）、易怒（7.3%）和行为障碍（5.3%）；12个月内，18.3%的PWE因AE导致治疗中断。AE的发生率以及因AE导致的停药率随年龄增加而升高（≥65岁的PWE中分别为55.0%和23.9%）。
在本项研究（迄今为止对PER临床实践数据进行的最大规模汇总分析）中，PER在日常临床实践中用于治疗局灶性或全身性癫痫患者时，无论年龄类别，均显示出有效性且总体耐受性良好。在现实环境中长期使用后未出现新的或意外的副作用。
