Perampanel as adjunctive therapy in highly refractory epilepsies: Real-world data from an Italian tertiary care epilepsy centre
Perampanel as adjunctive therapy in highly refractory epilepsies: Real-world data from an Italian tertiary care epilepsy centre
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DOI：
10.1016/j.jns.2018.04.017
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发表时间：
2018-07-15
影响因子：
4.4
通讯作者：
Di Bonaventura, Carlo
中科院分区：
文献类型：
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作者：
Morano, Alessandra;Fattouch, Jinane;Di Bonaventura, Carlo
Perampanel（PER）是一种选择性非竞争性α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体拮抗剂，获准用于局灶性癫痫和原发性全身强直阵挛性癫痫发作（pGTCS）的连续治疗。我们对接受PER治疗的高度难治性成人患者进行了一项回顾性研究，随访1年。留存率代表我们工作的主要结果;癫痫发作频率降低（>= 50%）、“转换率”和不良事件（AE）比例作为次要终点进行评估。纳入了89名受试者（47名女性，年龄范围：19-78岁）。其中局灶性癫痫73例，全身性癫痫9例，癫痫性脑病7例。所有患者均高度耐药（药物治疗失败：5-17）。3、6和12个月时的留存率分别为87.6%、63%和51.7%。应答者为27/89（30.3%），其中8/27例无复发。既往治疗失败的次数和同时使用酶诱导剂对临床应答产生负面影响，而PER剂量与结局之间无相关性。结构性癫痫的有效率（33%）高于病因不明的癫痫（20%），继发性GTCS的有效率（54%）高于局灶性癫痫（28%），而pGTCS的有效率（25%）较低。40%的患者报告了轻度至中度AE（主要是头晕、步态障碍和精神影响）;严重精神AE通常发生在患有精神病合并症的受试者中。我们的研究证实了PER在具有不同癫痫综合征和病因的高度耐药患者中的耐受性和有效性。
Perampanel (PER) is a selective non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist, licensed as adjunctive therapy in focal epilepsy and primary generalized tonic-clonic seizures (pGTCSs). We performed a retrospective study on highly refractory adult patients taking PER, with 1-year follow-up. Retention rate represented the primary outcome of our work; seizure frequency reduction (>= 50%), "switch rate" and proportion of adverse events (AEs) were evaluated as secondary endpoints. Eighty-nine subjects (47 females, age range: 19-78 years) were included. Seventy-three had focal epilepsy (FE), 9 generalized epilepsy and 7 epileptic encephalopathy. All patients were highly drug-resistant (medication failures: 5-17). Retention rate was 87.6%, 63% and 51.7% at 3, 6 and 12 months. Responders were 27/89 (30.3%), with 8/27 seizure-free. The number of previous treatment failures and the concomitant use of enzyme inducers negatively influenced clinical response, whereas no correlation was documented between PER dose and outcome. Responder proportion was more satisfying in structural FE than in FE of unknown etiology (33% versus 20%), and in secondarily GTCSs than focal seizures (54% vs 28%), whereas pGTCSs showed a lower reponse rate (25%). Mild-to-moderate AEs (mainly dizziness, gait disturbances and psychiatric effects) were reported by 40% of patients; serious psychiatric AEs usually occurred in subjects with psychiatric comorbidities. Our study confirms the tolerability and effectiveness of PER in highly drug-resistant patients with different epilepsy syndromes and aetiologies.