Department of Medicine, St Vincent's Hospital Melbourne, The University of Melbourne, Australia.
Department of Medicine, St Vincent's Hospital Melbourne, The University of Melbourne, Australia.
Epilepsy Behav. 2021 Jun;119:107935. doi: 10.1016/j.yebeh.2021.107935. Epub 2021 Apr 27.
To explore the efficacy and tolerability of adjuvant perampanel (PER) and their associated risk factors in late add-on drug-resistant epilepsy.
Retrospective multicenter 'real-world' observational study. Consecutively identified patients commenced on PER, with mixed epilepsy syndromes, from nine Australian epilepsy centers. Primary efficacy endpoints were at least 50% reduction in seizure frequency (responders), seizure freedom, and retention at 6 and 12 months, following a 3-month titration period. Tolerability endpoints were cessation of PER for any reason, cessation of PER due to treatment-emergent adverse events (TEAE), or cessation due to inefficacy. Outcomes were assessed for a-priori risk factors associated with efficacy and tolerability.
Three-hundred and eighty seven adults were identified and followed up for a median of 12.1 months (IQR 7.0-25.2). Focal epilepsy accounted for 79.6% (FE), idiopathic generalized epilepsy (IGE), 10.3% and developmental epileptic encephalopathy (DEE) 10.1%, of the cohort. All patients had drug-resistant epilepsy, 71.6% had never experienced six months of seizure freedom, and the mean number of antiepileptic medications (AEDs) prior to starting PER was six. At 12 months, with missing cases classified as treatment failure, retention was 40.0%, responder 21.7%, and seizure freedom 9.0%, whereas, using last outcome carried forward (LOCF), responder and seizure freedom rates were 41.3% and 14.7%, respectively. Older age of epilepsy onset was associated with a marginal increase in the likelihood of seizure freedom at 12-month maintenance (OR 1.04, 95% CI 1.02, 1.06). Male sex (adjusted OR [aOR] 2.06 95% CI 1.33, 3.19), lower number of prior AEDs (aOR 0.84, 95% CI 0.74, 0.96) and no previous seizure-free period of at least 6-month duration (aOR 2.04 95% CI 1.21, 3.47) were associated with retention. Perampanel combined with a GABA receptor AED was associated with a lower responder rate at 12 months but reduced cessation of PER. The most common TEAEs were neuropsychiatric (18.86%), followed by dizziness (13.70%), and sleepiness (5.68%).
Adjuvant PER treatment, even in late-add on drug-resistant epilepsy is an effective and well-tolerated treatment for drug-resistant epilepsy.
探索辅助性佩兰尼（PER）在晚期附加药物难治性癫痫中的疗效和耐受性及其相关的危险因素。
这是一项回顾性多中心“真实世界”观察性研究。在澳大利亚的 9 个癫痫中心，对混合癫痫综合征的患者进行了连续的 PER 辅助治疗。主要疗效终点为：在 3 个月的滴定期后，至少有 50%的癫痫发作频率减少（反应者）、无癫痫发作和 6 个月和 12 个月的保留率。耐受性终点为：因任何原因停止 PER、因治疗引起的不良反应（TEAE）而停止 PER，或因无效而停止 PER。对与疗效和耐受性相关的预先确定的风险因素进行了评估。
共确定了 387 名成年人，并对他们进行了中位时间为 12.1 个月（IQR 7.0-25.2）的随访。局灶性癫痫占 79.6%（FE），特发性全面性癫痫（IGE）占 10.3%，发育性癫痫性脑病（DEE）占 10.1%。所有患者均患有耐药性癫痫，71.6%的患者从未经历过 6 个月的无癫痫发作，在开始 PER 之前，他们平均使用的抗癫痫药物（AEDs）数量为 6 种。在 12 个月时，缺失病例被归类为治疗失败，保留率为 40.0%，反应者为 21.7%，无癫痫发作率为 9.0%，而使用最后一次结果外推（LOCF），反应者和无癫痫发作率分别为 41.3%和 14.7%。癫痫发作起始年龄较大与 12 个月维持期无癫痫发作的可能性略有增加相关（OR 1.04，95%CI 1.02，1.06）。男性（调整后的 OR [aOR] 2.06，95%CI 1.33，3.19）、较少的先前 AED 数量（aOR 0.84，95%CI 0.74，0.96）和没有至少 6 个月的无癫痫发作期（aOR 2.04，95%CI 1.21，3.47）与保留率相关。PER 联合 GABA 受体 AED 与 12 个月时的反应率较低相关，但减少了 PER 的停药率。最常见的不良事件为神经精神性（18.86%），其次为头晕（13.70%）和嗜睡（5.68%）。
辅助性 PER 治疗，即使在晚期附加药物难治性癫痫中，也是一种有效的、耐受性良好的耐药性癫痫治疗方法。
