Department of Medicine, St Vincent's Hospital Melbourne, The University of Melbourne, Australia.
Statistical Consulting Centre, The University of Melbourne, Australia.
Epilepsy Behav. 2020 Mar;104(Pt A):106883. doi: 10.1016/j.yebeh.2019.106883. Epub 2020 Feb 8.
The objective of this study was to evaluate the efficacy and tolerability of perampanel (PER) in late adjunctive treatment of focal epilepsy. We assessed outcomes 1) according to patients' clinical profiles and the broad mechanism of action (MoA) of concomitant antiepileptic drugs (AEDs) and 2) the effects of PER on adverse events, irritability, mood, and quality of life (QOL).
Consecutive patients commenced on PER at two epilepsy centers in Melbourne, Australia were identified. A nested cohort underwent detailed prospective assessment, while the remainder were retrospectively analyzed. Six- and 12-month efficacy endpoints were at least a 50% reduction in seizure frequency (responders) and complete seizure freedom. The prospective cohort underwent standardized validated questionnaires at 0, 1, 3, 6, and 12 months using the modified semi-structured seizure interview (SSI), Liverpool Adverse Events Profile (LAEP), Quality of Life in Epilepsy-Patient-Weighted (QOLIE-10-P), Neurological Disorders Depression Inventory Epilepsy (NDDI-E), and an Irritability Questionnaire.
One hundred sixty patients were followed for a median of 6 months: the mean number of prior AEDs was 6, 99% had drug-resistant epilepsy, and 72% had never experienced a prior seizure-free period of at least 6 months (=continuously refractory epilepsy). Perampanel was associated with responder and seizure freedom rates of 30.6% and 9.4% at 6 months and 19.4% and 4.4% (5.6% adjusted for the titration period) at 12 months. Having "continuously refractory epilepsy" was associated with a reduced likelihood of seizure freedom at 6 months (5% vs. 30%; p = 0.001) and 12 months (3% vs. 13%; p = 0.058). Quality of Life in Epilepsy-Patient-Weighted, irritability, and NDDI-E showed mean improvement at 6 months from baseline.
Even when used as late add-on adjunctive therapy in patients with highly refractory focal epilepsy, PER can result in 12-month seizure freedom of 5.6%. The likelihood of seizure freedom was associated with prior "continuous medication refractoriness". Six months after introduction of PER patients reported improved mood, QOL, and decreased irritability.
本研究旨在评估吡仑帕奈（PER）在局灶性癫痫辅助治疗晚期的疗效和耐受性。我们根据患者的临床特征和伴随抗癫痫药物（AEDs）的广泛作用机制（MoA），评估了 1）疗效，2）PER 对不良事件、易激惹、情绪和生活质量（QOL）的影响。
在澳大利亚墨尔本的两个癫痫中心确定了开始使用 PER 的连续患者。一个嵌套队列进行了详细的前瞻性评估，而其余队列则进行了回顾性分析。6 个月和 12 个月的疗效终点是至少减少 50%的发作频率（应答者）和完全无发作。前瞻性队列在 0、1、3、6 和 12 个月使用改良半结构化发作访谈（SSI）、利物浦不良事件概况（LAEP）、癫痫患者生活质量量表（QOLIE-10-P）、神经障碍抑郁量表癫痫（NDDI-E）和易激惹问卷进行标准化验证。
160 例患者中位随访时间为 6 个月：平均使用 AEDs 数为 6，99%为难治性癫痫，72%从未经历过至少 6 个月的无发作期（=持续难治性癫痫）。PER 在 6 个月时的应答率和无发作率分别为 30.6%和 9.4%，12 个月时分别为 19.4%和 4.4%（调整滴定期后为 5.6%）。“持续难治性癫痫”与 6 个月（5%对 30%；p=0.001）和 12 个月（3%对 13%；p=0.058）无发作率降低相关。癫痫患者生活质量量表、易激惹和神经障碍抑郁量表癫痫在 6 个月时与基线相比平均有所改善。
即使在具有高度难治性局灶性癫痫的患者中作为晚期辅助添加治疗，PER 也可以在 12 个月内达到 5.6%的无发作率。无发作的可能性与先前的“连续药物耐药性”相关。PER 引入 6 个月后，患者报告情绪、QOL 改善，易激惹减少。
