目的:大麻二酚(CBD)扩大获取计划为治疗难治性癫痫患者提供了富有同情心的CBD获取途径,包括结节性硬化症(TSC),在35个美国癫痫中心。这里,我们介绍了TSC患者附加CBD治疗的长期疗效和安全性结局.
方法:患者接受植物来源,高度纯化的CBD(Epidiolex®100mg/mL,口服溶液),从2到10mg/kg/d增加到耐受或最大25-50mg/kg/d。疗效终点是自基线的变化百分比,在平均每月惊厥,焦点,和总发作频率≥50%,≥75%,在144周内的12周访问窗口中,100%的应答率。不良事件(AE)报告至233周。
结果:纳入34例TSC确诊患者。平均年龄为12.4岁(范围,1.8-31.2),患者接受的中位数为3(范围,1-7)基线时的抗癫痫药物(ASM)。CBD的中位剂量为25-28mg/kg/d,持续36周,然后为20-50mg/kg/d,持续228周。大多数ASM的剂量从基线减少,除了托吡酯.抽搐频率的中间减少,焦点,总缉获量为44%-81%,51%-87%,44%-87%,分别,144周响应速率(≥50%,≥75%,和100%减少)为43%-71%,14%-58%,惊厥性癫痫发作为0%-25%;52%-75%,35%-60%,局灶性癫痫发作为7%-32%;46%-79%,26%-65%,和0%-13%的总癫痫发作。总共94%的患者经历了≥1次AE;47%有严重的AE,研究者认为治疗无关。71%的患者发生治疗相关的AE(TRAE)。最常报告的TRAEs是嗜睡,腹泻,和共济失调.两名患者经历了导致停药的AE。没有死亡。
结论:长期使用CBD与144周癫痫发作频率降低相关。安全性与以前的报告一致。
结论:在这项研究中,我们评估了大麻二酚(CBD)治疗结节性硬化症患者的疗效和安全性,该患者除了接受其他抗癫痫治疗外还接受CBD治疗.开始CBD后,46%-79%的患者每月癫痫发作次数至少减少50%,26%-65%的患者每月癫痫发作次数至少减少75%;高达13%的患者在144周内没有癫痫发作。安全性结果与先前的研究相似;嗜睡和腹泻是常见的治疗相关副作用。这些结果表明,长期CBD治疗与较少的癫痫发作和轻度/中度副作用有关。
OBJECTIVE: The cannabidiol (CBD) Expanded Access Program provided compassionate access to CBD for patients with treatment-resistant epilepsy, including tuberous sclerosis complex (TSC), at 35 US epilepsy centers. Here, we present the long-term efficacy and safety outcomes for add-on CBD treatment in patients with TSC.
METHODS: Patients received plant-derived, highly purified CBD (Epidiolex® 100 mg/mL, oral solution), increasing from 2 to 10 mg/kg/d to tolerance or maximum of 25-50 mg/kg/d. Efficacy endpoints were percentage change from baseline in median monthly convulsive, focal, and total seizure frequency and ≥ 50%, ≥75%, and 100% responder rates across 12-week visit windows through 144 weeks. Adverse events (AEs) are reported through 233 weeks.
RESULTS: Thirty-four patients with confirmed TSC were included. Mean age was 12.4 years (range, 1.8-31.2), and patients were receiving a median of 3 (range, 1-7) antiseizure medications (ASMs) at baseline. Median CBD dose was 25-28 mg/kg/d for 36 weeks and then 20-50 mg/kg/d through 228 weeks. Dose reduction from baseline occurred for most ASMs, except topiramate. Median reduction in the frequency of convulsive, focal, and total seizures was 44%-81%, 51%-87%, and 44%-87%, respectively, through 144 weeks. Responder rates (≥50%, ≥75%, and 100% reduction) were 43%-71%, 14%-58%, and 0%-25% for convulsive seizures; 52%-75%, 35%-60%, and 7%-32% for focal seizures; and 46%-79%, 26%-65%, and 0%-13% for total seizures. A total of 94% of patients experienced ≥1 AE; 47% had serious AEs, considered treatment unrelated by the investigator. Treatment-related AEs (TRAEs) occurred in 71% of patients. The most frequently reported TRAEs were somnolence, diarrhea, and ataxia. Two patients experienced AEs leading to discontinuation. There were no deaths.
CONCLUSIONS: Long-term add-on CBD use was associated with reduced seizure frequency through 144 weeks. The safety profile was consistent with previous reports.
CONCLUSIONS: In this study, we evaluated efficacy and safety of cannabidiol (CBD) treatment in patients with tuberous sclerosis complex receiving CBD in addition to other antiseizure treatments in an Expanded Access Program. After starting CBD, 46%-79% of patients had at least 50% reduction and 26%-65% had at least 75% reduction in the number of seizures per month; up to 13% had no seizures through 144 weeks. Safety results were similar to prior studies; sleepiness and diarrhea were common treatment-related side effects. These results show that long-term CBD treatment was associated with fewer seizures and mild/moderate side effects.