Hospital Universitario y Politécnico La Fe, Valencia, Spain.
Hospital Clínico Universitario, Madrid, Spain.
Epilepsy Behav. 2022 Dec;137(Pt A):108958. doi: 10.1016/j.yebeh.2022.108958. Epub 2022 Oct 29.
To evaluate the effectiveness and tolerability of cannabidiol (CBD) in patients with developmental and epileptic encephalopathies, including Dravet syndrome (DS), and Lennox-Gastaut syndrome (LGS), in a Spanish Expanded Access Program (EAP).
This was a multicenter, retrospective, observational study of patients treated with purified CBD in 14 hospitals across Spain. Patients with (1) written informed consent and (2) at least 6 months follow-up before the closure of the database were included. Primary effectiveness endpoints included reductions (100 %, ≥75 %, ≥50 %, ≥25 %, or 0 %) or worsening in seizure frequency (all seizure types and most disabling seizures) at 1-, 3-, 6-, and 12-month visits and at the last visit, and median relative seizure reduction between baseline and last visit. Secondary effectiveness endpoints included retention rate, reduction in seizure severity, status epilepticus, healthcare utilization, and quality of life. Primary safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation.
One hundred and two patients (DS 12 %; LGS 59 %; other epilepsy syndromes 29 %) with a mean age of 15.9 years were enrolled. Patients were highly refractory to antiseizure medications (ASMs); mean number of prior failed ASMs was 7.5 (SD 3.7). The mean CBD dose was 13.0 mg/kg/day at the last visit. The proportion of patients with ≥50 % reduction in the total number of seizures from baseline was 44.9 % at 6 months and 38.9 % at 12 months. The median number of total seizures per month reduced by 47.6 % from baseline to the last visit. At 12 months, seizure severity was lower in 33/54 patients (61.1 %) and unchanged in 17/54 patients (31.5 %). Quality of life, based on the CAVE scale, increased from a mean score of 17.9 ± 4.7 (n = 54) at baseline to 21.7 ± 5.5 (n = 51) at the last patient visit (21.2 % improvement). The mean treatment retention time was 10.3 months. There were no statistically significant changes in the number of status epilepticus episodes, but lower healthcare utilization was observed. Adverse events occurred in sixty-eight patients (66.7 %), and the most common were somnolence (34.3 %) and diarrhea (12.7 %). Cannabidiol was discontinued exclusively due to AEs in 7.8 % of patients, increasing to 25.5 % when both lack of efficacy and AEs were considered together.
Cannabidiol demonstrated promising effectiveness and tolerability in patients with developmental and epileptic encephalopathies taking part in a Spanish EAP.
评估大麻二酚（CBD）在包括德拉维特综合征（DS）和 Lennox-Gastaut 综合征（LGS）在内的发育性和癫痫性脑病患者中的有效性和耐受性，该研究是在西班牙的一项扩展准入计划（EAP）中进行的。
这是一项多中心、回顾性、观察性研究，纳入了在西班牙 14 家医院接受纯化 CBD 治疗的患者。纳入标准为：（1）签署书面知情同意书；（2）在数据库关闭前至少有 6 个月的随访。主要有效性终点包括在第 1、3、6 和 12 个月访视以及最后一次访视时的癫痫发作频率（所有癫痫发作类型和最致残的癫痫发作）减少（100%、≥75%、≥50%、≥25%或 0%）或恶化，以及从基线到最后一次访视的中位相对癫痫发作减少。次要有效性终点包括保留率、癫痫严重程度的降低、癫痫持续状态、医疗保健利用和生活质量。主要安全性终点包括不良事件（AE）和导致停药的 AE 的发生率。
共纳入 102 名患者（DS 12%；LGS 59%；其他癫痫综合征 29%），平均年龄为 15.9 岁。患者对抗癫痫药物（ASM）高度耐药；平均既往失败 ASM 数量为 7.5（SD 3.7）。最后一次就诊时 CBD 平均剂量为 13.0mg/kg/天。6 个月时有 44.9%的患者总癫痫发作次数减少≥50%，12 个月时有 38.9%的患者总癫痫发作次数减少≥50%。从基线到最后一次就诊，每月总癫痫发作次数减少了 47.6%。12 个月时，54 名患者中有 33 名（61.1%）癫痫严重程度降低，17 名（31.5%）不变。基于 CAVE 量表，生活质量从基线时的平均得分 17.9±4.7（n=54）增加到最后一次就诊时的 21.7±5.5（n=51）（21.2%的改善）。平均治疗保留时间为 10.3 个月。癫痫持续状态发作次数无统计学意义的变化，但观察到医疗保健利用率降低。68 名患者（66.7%）出现不良事件，最常见的是嗜睡（34.3%）和腹泻（12.7%）。由于 AE，仅 7.8%的患者停止使用 CBD，当同时考虑缺乏疗效和 AE 时，这一比例增加到 25.5%。
在参加西班牙 EAP 的发育性和癫痫性脑病患者中，大麻二酚显示出有希望的有效性和耐受性。
