比较分析老年（≥60 岁）和年轻（18-59 岁）成年人中依佐加滨醋酸酯的安全性和耐受性。
Comparative analysis of the safety and tolerability of eslicarbazepine acetate in older (≥60 years) and younger (18-59 years) adults.
机构信息
Neurogenetics Unit and Epilepsy Research Group, Montreal Neurological Institute and Hospital, Departments of Neurology & Neurosurgery and Human Genetics, McGill University, Montreal, QC, Canada.
The Comprehensive Epilepsy Care Center for Children and Adults, St Louis, MO, USA.
出版信息
Epilepsy Res. 2021 Jan;169:106478. doi: 10.1016/j.eplepsyres.2020.106478. Epub 2020 Oct 10.
OBJECTIVE
To investigate the safety and tolerability of eslicarbazepine acetate (ESL), a once-daily oral anti-seizure drug (ASD), in older and younger adult patient populations.
METHODS
Two post-hoc pooled data analyses were performed: one from three Phase III studies in patients with focal (partial-onset) seizures who were taking 1-3 concomitant ASDs; the other from five Phase II studies in patients from non-epilepsy populations not taking other ASDs chronically and/or at a clinically-effective anti-seizure dose. The frequencies of treatment-emergent adverse events (TEAEs) were calculated for the older (≥60 years) and younger (18-59 years) adults separately.
RESULTS
In the focal seizures study pool, 4.1 % of patients (58/1431) were aged ≥60 years. The overall frequency of TEAEs was 77.5 % in older ESL-treated patients and 72.6 % in younger ESL-treated patients (p = 0.495). For patients who received placebo, the overall frequency of TEAEs was 50.0 % in the older adults and 57.5 % in the younger adults (p = 0.531). The overall placebo-adjusted frequency of TEAEs was 27.5 % in older adults and 15.1 % in younger adults. The placebo-adjusted frequencies of the TEAEs dizziness, somnolence, headache, nausea, diplopia, blurred vision, and ataxia were ≥5 % higher, and frequencies of vomiting and vertigo were ≥2 % higher in older than younger adults. The overall frequency of TEAEs leading to discontinuation was 15.0 % in older ESL-treated patients and 17.6 % in younger ESL-treated patients (p = 0.647); the frequency increased with increasing ESL dose. For patients who received placebo, the overall frequency of TEAEs leading to discontinuation was 5.6 % in older adults and 6.6 % in younger adults (p = 0.847). In the non-epilepsy study pool, 30.2 % of patients (515/1705) were aged ≥60 years. The overall frequency of TEAEs was 56.9 % in older ESL-treated patients and 58.8 % in younger ESL-treated patients. The placebo-adjusted frequencies were 14.9 % in older and 15.1 % in younger ESL-treated patients. The placebo-adjusted frequencies of the TEAEs nausea, vomiting, fatigue, and vertigo were ≥2 % higher in older adults, whereas somnolence was ≥2 % higher in younger adults. The overall frequency of TEAEs leading to discontinuation was 18.3 % in older ESL-treated patients and 12.1 % in younger ESL-treated patients (p = 0.003); frequencies were not related to ESL dose. For patients who received placebo, the overall frequency of TEAEs leading to discontinuation was 8.0 % in older adults and 5.6 % in younger adults (p = 0.407).
CONCLUSION
Analyses of adverse event data support the safety and tolerability of ESL in adults aged ≥60 years. In the limited number of older patients with focal seizures taking ESL plus concomitant ASDs (n = 40), the frequency of TEAEs was generally higher than in younger adults. However, in the non-epilepsy patient group (in which the number of older patients was ten times larger; 427 patients taking ESL without concomitant ASDs), no marked age-related TEAE differences were observed, suggesting that increased ASD load associated with adjunctive therapy may complicate treatment selection in older patients, due to risk of increased adverse events. As is common practice for all ASDs, balancing clinical response and tolerability is needed in this vulnerable group of patients.
目的
研究艾司利卡西平醋酸盐（ESL）作为一种每日一次的口服抗癫痫药物（ASD）在老年和年轻成年患者人群中的安全性和耐受性。
方法
进行了两项事后汇总数据分析：一项来自三项 III 期研究，这些研究纳入了服用 1-3 种合并 ASD 的局灶性（部分性发作）癫痫患者；另一项来自五项非癫痫患者人群的 II 期研究，这些患者未长期服用其他 ASD 且/或未服用临床有效剂量的 ASD。分别计算老年（≥60 岁）和年轻（18-59 岁）成年患者中治疗出现的不良事件（TEAE）的频率。
结果
在局灶性癫痫研究中，4.1%（58/1431）的患者年龄≥60 岁。老年 ESL 治疗患者的总体 TEAE 频率为 77.5%，年轻 ESL 治疗患者为 72.6%（p=0.495）。接受安慰剂的患者中，老年患者的总体 TEAE 频率为 50.0%，年轻患者为 57.5%（p=0.531）。安慰剂调整后的 TEAE 总体频率在老年患者中为 27.5%，在年轻患者中为 15.1%。安慰剂调整后的头晕、嗜睡、头痛、恶心、复视、视力模糊和共济失调的 TEAE 频率在老年患者中≥5%更高，而呕吐和眩晕的 TEAE 频率在老年患者中≥2%更高。老年 ESL 治疗患者因 TEAE 停药的总体频率为 15.0%，年轻 ESL 治疗患者为 17.6%（p=0.647）；随着 ESL 剂量的增加，频率也随之增加。接受安慰剂的患者中，因 TEAE 停药的总体频率在老年患者中为 5.6%，年轻患者中为 6.6%（p=0.847）。在非癫痫研究中，30.2%（515/1705）的患者年龄≥60 岁。老年 ESL 治疗患者的总体 TEAE 频率为 56.9%，年轻 ESL 治疗患者为 58.8%。安慰剂调整后的频率在老年患者中为 14.9%，在年轻患者中为 15.1%。老年患者中恶心、呕吐、疲劳和眩晕的 TEAE 频率安慰剂调整后≥2%更高，而年轻患者中嗜睡的 TEAE 频率安慰剂调整后≥2%更高。老年 ESL 治疗患者因 TEAE 停药的总体频率为 18.3%，年轻 ESL 治疗患者为 12.1%（p=0.003）；频率与 ESL 剂量无关。接受安慰剂的患者中，老年患者因 TEAE 停药的总体频率为 8.0%，年轻患者为 5.6%（p=0.407）。
结论
不良事件数据的分析支持 ESL 在≥60 岁成年患者中的安全性和耐受性。在服用 ESL 加合并 ASD 的局灶性癫痫老年患者（n=40）中，TEAE 的频率通常高于年轻患者。然而，在非癫痫患者组（服用 ESL 且无合并 ASD 的患者数量是前者的十倍，为 427 例）中，未观察到明显的年龄相关 TEAE 差异，这表明由于不良反应风险增加，与辅助治疗相关的 ASD 负荷增加可能会使老年患者的治疗选择复杂化。与所有 ASD 一样，在这一脆弱患者群体中，需要平衡临床反应和耐受性。
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