University of Cincinnati Medical Center, Cincinnati, OH, USA.
Neurocenter Barcelona, Teknon Medical Center, Barcelona, Spain.
Epilepsia. 2021 May;62(5):1130-1140. doi: 10.1111/epi.16878. Epub 2021 Apr 2.
To estimate time to onset of cannabidiol (CBD) treatment effect (seizure reduction and adverse events [AEs]), we conducted post hoc analyses of data from two randomized, placebo-controlled, Phase 3 trials, GWPCARE3 (NCT02224560) and GWPCARE4 (NCT02224690), of patients with Lennox-Gastaut syndrome.
Patients received plant-derived pharmaceutical formulation of highly purified CBD (Epidiolex, 100 mg/ml oral solution) at 10 mg/kg/day (CBD10; GWPCARE3) or 20 mg/kg/day (CBD20; both trials) or placebo for 14 weeks. Treatment started at 2.5 mg/kg/day for all groups and reached 10 mg/kg/day on Day 7 and 20 mg/kg/day (CBD20 and matching placebo only) on Day 11. Percentage change from baseline in drop seizure frequency was calculated by cumulative day (i.e., including all previous days). Time to onset and resolution of AEs were evaluated.
Overall, 235 patients received CBD (CBD10 [GWPCARE3 only], n = 67; CBD20 [pooled GWPCARE3&4], n = 168) and 161 received placebo. Mean (range) age was 15.3 years (2.6-48.0). Patients had previously discontinued a median (range) of six (0-28) antiepileptic drugs (AEDs) and were currently taking a median of three (0-5) AEDs. Differences in drop seizure reduction between placebo and CBD emerged during the titration period and became nominally significant by Day 6 (p = .008) for pooled CBD treatment groups. Separation between placebo and CBD in ≥50% responder rate emerged by Day 6. Onset of the first reported AE occurred during the titration period in 45% of patients (CBD10, 46%; CBD20, 52%; placebo, 38%). In patients with AEs, resolution occurred within 4 weeks of onset in 53% of placebo and 39% of CBD patients and by end of study in 63% of placebo and 61% of CBD patients.
Treatment effect (efficacy and AEs) of CBD may occur within 1 week of starting treatment. Although AEs lasted longer for CBD than placebo, most resolved within the 14-week period.
通过对两项随机、安慰剂对照、3 期 GWPCARE3（NCT02224560）和 GWPCARE4（NCT02224690）临床试验的事后分析，估计大麻二酚（CBD）治疗起效时间（癫痫发作减少和不良事件[AE]），这些试验入组了患有 Lennox-Gastaut 综合征的患者。
患者接受植物源高纯度 CBD（Epidiolex，100mg/ml 口服溶液）10mg/kg/天（CBD10；GWPCARE3）或 20mg/kg/天（CBD20；两项试验）或安慰剂治疗 14 周。所有组均以 2.5mg/kg/天起始治疗，第 7 天达到 10mg/kg/天，第 11 天达到 20mg/kg/天（仅 CBD20 和匹配安慰剂）。通过累积天数（即包括所有之前的天数）计算基线时癫痫发作频率的百分比变化。评估 AE 的起始时间和解决情况。
总体而言，235 例患者接受了 CBD（仅 GWPCARE3 的 CBD10[n=67]；GWPCARE3 和 4 的 CBD20[n=168]），161 例患者接受了安慰剂。患者的平均（范围）年龄为 15.3 岁（2.6-48.0）。患者此前平均（范围）已停用六种（0-28）种抗癫痫药物（AED），目前平均使用三种（0-5）种 AED。在滴定期间，安慰剂和 CBD 之间在癫痫发作减少方面的差异显现，在第 6 天（p=0.008）对 CBD 联合治疗组具有名义显著性。在第 6 天，出现了安慰剂和 CBD 之间≥50%应答率的分离。第 1 次报告的 AE 发生在滴定期间，45%的患者（CBD10，46%；CBD20，52%；安慰剂，38%）出现这种情况。在有 AE 的患者中，53%的安慰剂和 39%的 CBD 患者在 AE 发生后 4 周内得到解决，63%的安慰剂和 61%的 CBD 患者在研究结束时得到解决。
CBD 的治疗效果（疗效和 AE）可能在开始治疗后 1 周内显现。尽管 CBD 的 AE 持续时间长于安慰剂，但大多数在 14 周内得到解决。
