Cannabidiol efficacy independent of clobazam: Meta-analysis of four randomized controlled trials.
Cannabidiol efficacy independent of clobazam: Meta-analysis of four randomized controlled trials.
复制标题
DOI：
10.1111/ane.13305
复制
发表时间：
2020-12
影响因子：
3.5
通讯作者：
Knappertz V
中科院分区：
文献类型：
--
作者：
Devinsky O;Thiele EA;Wright S;Checketts D;Morrison G;Dunayevich E;Knappertz V
在4项大型随机对照试验（2项在伦诺克斯-Gastaut综合征中，2项在Dravet综合征中）的分层分析中评价了大麻二酚（CBD）与氯巴占（CLB）合并或不合并的疗效。CBD的每个试验（Epidiolex®在美国; Epidyolex®在欧盟; 10和20 mg/kg/天）通过CLB使用进行评估。使用负二项回归分析癫痫发作频率的变化和logistic回归分析50%应答率，其中主要分析在分层Meta分析中结合了适应症和CBD剂量。基于CLB存在/不存在，检查药代动力学数据的暴露/反应关系。使用描述性统计分析安全性数据。Meta分析支持CBD与安慰剂，无论CLB使用如何。CBD与安慰剂相比，癫痫发作频率平均降低的治疗比（95% CI）为0.59（0.52，0.68; P < .0001），CLB和0.85（0.73，0.98; P = .0226），50%应答率比值比（95%CI）为2.51（1.69，3.71; P < .0001），无CLB时为2.40（1.38，4.16; P = .0020）。与嗜睡、皮疹、肺炎或攻击性相关的不良事件（AE）在伴随CLB的患者中更常见。CBD及其活性代谢物存在显著的暴露/反应关系。这些结果表明CBD在有和没有CLB的情况下是有效的，但不排除与药剂组合相关的协同效应的可能性。没有CLB的CBD的安全性和耐受性特征显示某些AE的发生率低于CLB。
The efficacy of cannabidiol (CBD) with and without concomitant clobazam (CLB) was evaluated in stratified analyses of four large randomized controlled trials, two in Lennox‐Gastaut syndrome, and two in Dravet syndrome. Each trial of CBD (Epidiolex® in the US; Epidyolex® in the EU; 10 and 20 mg/kg/day) was evaluated by CLB use. The treatment ratio was analyzed using negative binomial regression for changes in seizure frequency and logistic regression for the 50% responder rate, where the principle analysis combined both indications and CBD doses in a stratified meta‐analysis. Pharmacokinetic data were examined for an exposure/response relationship based on CLB presence/absence. Safety data were analyzed using descriptive statistics. The meta‐analysis favored CBD vs. placebo regardless of CLB use. The treatment ratio (95% CI) of CBD over placebo for the average reduction in seizure frequency was 0.59 (0.52, 0.68; P < .0001) with CLB and 0.85 (0.73, 0.98; P = .0226) without CLB, and the 50% responder rate odds ratio (95% CI) was 2.51 (1.69, 3.71; P < .0001) with CLB and 2.40 (1.38, 4.16; P = .0020) without CLB. Adverse events (AEs) related to somnolence, rash, pneumonia, or aggression were more common in patients with concomitant CLB. There was a significant exposure/response relationship for CBD and its active metabolite. These results indicate CBD is efficacious with and without CLB, but do not exclude the possibility of a synergistic effect associated with the combination of agents. The safety and tolerability profile of CBD without CLB show a lower rate of certain AEs than with CLB.
登录
查看更多内容
影响因子：
158.5
作者：
Devinsky, Orrin;Patel, Anup D.;Zuberi, Sameer M.
通讯作者：
Zuberi, Sameer M.
影响因子：
168.9
作者：
Thiele, Elizabeth A.;Marsh, Eric D.;Sommerville, Kenneth
通讯作者：
Sommerville, Kenneth
影响因子：
5.6
作者：
Gaston, Tyler E.;Bebin, E. Martina;Szaflarski, Jerzy P.
通讯作者：
Szaflarski, Jerzy P.
影响因子：
5.6
作者：
Geffrey, Alexandra L.;Pollack, Sarah F.;Thiele, Elizabeth A.
通讯作者：
Thiele, Elizabeth A.
DOI：
10.1016/j.yebeh.2016.11.006
发表时间：
2017-05
期刊：
Epilepsy & behavior : E&B
影响因子：
--
作者：
Rosenberg EC;Patra PH;Whalley BJ
通讯作者：
Whalley BJ