Massachusetts General Hospital, Boston, Massachusetts, USA.
University of Alabama School of Medicine, Birmingham, Alabama, USA.
Epilepsia. 2022 Feb;63(2):426-439. doi: 10.1111/epi.17150. Epub 2021 Dec 27.
To evaluate the long-term safety and efficacy of add-on cannabidiol (CBD) in patients with seizures associated with tuberous sclerosis complex (TSC) in the open-label extension (OLE) of the randomized, placebo-controlled phase 3 trial GWPCARE6 (NCT02544763). Results of an interim (February 2019 data cut) analysis are reported.
Patients who completed the randomized trial enrolled to receive CBD (Epidiolex in the United States; Epidyolex in the EU; 100 mg/mL oral solution). The initial target dose was 25 mg/kg/day, which, based on response and tolerability, could be decreased or increased up to 50 mg/kg/day. The primary end point was safety. Key secondary end points included percentage reduction in TSC-associated (countable focal and generalized) seizures, responder rates, and Subject/Caregiver Global Impression of Change (S/CGIC).
Of 201 patients who completed the randomized phase, 199 (99%) entered the OLE. Mean age was 13 years (range, 1-57). At the time of analysis, 5% of patients had completed treatment, 20% had withdrawn, and 75% were ongoing. One-year retention rate was 79%. Median treatment time was 267 days (range, 18-910) at a 27 mg/kg/day mean modal dose. Most patients (92%) had an adverse event (AE). Most common AEs were diarrhea (42%), seizure (22%), and decreased appetite (20%). AEs led to permanent discontinuation in 6% of patients. There was one death that was deemed treatment unrelated by the investigator. Elevated liver transaminases occurred in 17 patients (9%) patients; 12 were taking valproate. Median percentage reductions in seizure frequency (12-week windows across 48 weeks) were 54%-68%. Seizure responder rates (≥50%, ≥75%, 100% reduction) were 53%-61%, 29%-45%, and 6%-11% across 12-week windows for 48 weeks. Improvement on the S/CGIC scale was reported by 87% of patients/caregivers at 26 weeks.
In patients with TSC, long-term add-on CBD treatment was well tolerated and sustainably reduced seizures through 48 weeks, with most patients/caregivers reporting global improvement.
评估在随机、安慰剂对照的 3 期试验 GWPCARE6（NCT02544763）的开放标签扩展（OLE）中，添加治疗用大麻二酚（CBD）对伴有结节性硬化症（TSC）的癫痫发作患者的长期安全性和疗效。报道了中期（2019 年 2 月数据截止）分析的结果。
完成随机试验的患者入组接受 CBD（美国的 Epidiolex；欧盟的 Epidyolex；100mg/mL 口服溶液）治疗。初始目标剂量为 25mg/kg/天，根据反应和耐受性，剂量可降低或增加至 50mg/kg/天。主要终点是安全性。主要次要终点包括 TSC 相关（可计数局灶性和全身性）癫痫发作减少百分比、应答率和患者/照护者变化总体印象（S/CGIC）。
201 例完成随机阶段的患者中，199 例（99%）进入 OLE。平均年龄为 13 岁（范围，1-57）。在分析时，5%的患者已完成治疗，20%的患者已停药，75%的患者仍在接受治疗。1 年保留率为 79%。中位治疗时间为 267 天（范围，18-910），平均剂量为 27mg/kg/天。大多数患者（92%）发生了不良事件（AE）。最常见的 AEs 为腹泻（42%）、癫痫（22%）和食欲下降（20%）。AE 导致 6%的患者永久停药。有 1 例死亡被研究者认为与治疗无关。17 例（9%）患者出现肝转氨酶升高；其中 12 例正在服用丙戊酸钠。在 48 周的 12 周时间窗内，癫痫发作频率的中位数降低率为 54%-68%。在 48 周的 12 周时间窗内，癫痫发作应答率（≥50%、≥75%、100%减少）分别为 53%-61%、29%-45%和 6%-11%。在 26 周时，87%的患者/照护者报告了 S/CGIC 量表的改善。
在 TSC 患者中，长期添加 CBD 治疗耐受性良好，可在 48 周内持续减少癫痫发作，大多数患者/照护者报告整体改善。
