Patients who were treated with cannabidiol 25 mg or 50 mg experienced seizure reductions of 49% and 48%, respectively, nearly double that of the placebo group, which experienced reductions of 27%.
Elizabeth Thiele, MD, PhD
Data suggest that cannabidiol (CBD, Epidiolex; GW Pharmaceuticals) can significantly reduce seizures associated with tuberous sclerosis complex (TSC), with similar efficacy observed between lower and higher doses.1
All told, those treated with CBD experienced reductions in TSC-associated seizure frequency of 49% with the 25 mg/kg dose and 48% for the 50 mg/kg dose, nearly double that of the placebo group, which experienced reductions of 27% (25 mg: P = .0009; 50 mg: P = .0018).
The data from the GWPCARE6 trial were presented by Elizabeth Thiele, MD, PhD, director, pediatric epilepsy and the Herscot Center for Tuberous Sclerosis Complex, Massachusetts General Hospital, and professor of neurology, Harvard Medical School, at the 73rd annual meeting of the American Epilepsy Society (AES), December 6-10, 2019, in Baltimore, Maryland.2
“Our findings suggest this formulation of purified CBD offers patients with TSC a new treatment option for their very difficult-to-manage seizures,” Thiele said in a statement. “We also assessed 2 different daily doses and found the lower dose of 25 mg/kg of weight provides the same benefit with fewer side effects compared to a dose of 50 mg/kg and will likely be the recommended dose.”
GWPCARE6 included a total of 224 patients, with 75 randomized to the 25 mg group, 73 to the 25 mg group, and 76 to placebo. Overall, 201 patients completed the study. The median (range) age was 11 years, with a median baseline monthly TSC-associated seizure frequency of 56 (interquartile range [IQR], 21—101) for the 25 mg group, 61 (IQR, 36–117) for the 50 mg group, and 54 (IQR, 26–102) for placebo.
Patients had previously tried and discontinued a median of 4 antiepileptic drugs and were currently taking a mean of 3. The most common concomitant drugs were valproate (45%), vigabatrin (33%), levetiracetam (29%), and clobazam (27%).
Those who took CBD were more likely to experience a ≥50% reduction in seizures, observed in 36% of the 25 mg group (P = .0692) and 40% of the 50 mg group (P = .0245) compared to 22% for placebo. Caregivers reported an overall improvement in 69% of those taking 25 mg of CBD, 62% of those taking 50 mg and 40% of those who received placebo.
The CBD groups also saw significantly greater reduction in total seizure frequency compared to placebo: 48% for 25 mg (P = .0013), 48% for 50 mg (P = .0018), and 27% for placebo. Improvement in overall condition on the Clinical Global Impression of Change (CGIC) was reported by 69% (odds ratio [OR], 2.25; P = .0074) of patients/caregivers for the 25 mg group and 62% (OR, 1.77; P = .0580) for 50 mg, compared to 40% for placebo.
“Studies show that the benefits of CBD treatment can last up to 6 years, with no changes in safety,” Thiele said. “Physicians are finding that CBD may be helpful for other treatment-resistant epilepsies as well, including Aicardi, Doose, CDKL5 andDup15q.”
Adverse events (AEs) were common, occurring at a rate of 93% in the 25 mg group, 100% of the 50 mg group, and 95% of placebo group, though the majority were deemed mild or moderate. The most common included diarrhea (25 mg: 31%; 50 mg: 56%; placebo: 25%), decreased appetite (25 mg: 20%; 50 mg: 23%; placebo: 12%), and somnolence (25 mg: 13%; 50 mg: 26%; placebo: 9%).
Discontinuation of treatment due to AEs occurred in 11% of the 25 mg group, 14% of the 50 mg group, and 3% of placebo patients. As well, 12% of the 25 mg patients (n = 9) and 25% of the 50 mg patients (n = 18) had elevated liver enzymes. Of those, 81% were also taking valproate.
CBD was first approved in June 2018 as Epidiolex, making it the first drug approved by the FDA to contain a marijuana-derived, purified drug substance, as well as the first for the treatment of patients with Dravet syndrome. It is currently indicated for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome in those 2 years of age and older.
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1. Thiele E, Wong M. Cannabidiol (CBD) treatment in patients with seizures associated with tuberous sclerosis complex: a randomized, double-blind, placebo-controlled phase 3 trial (GWPCARE6). Presented at: AES 2019; December 7—10; Baltimore, Maryland. Abstract 1.293.
2. Trial Shows CBD Helpful for Tuberous Sclerosis Complex-related Seizures, May Expand Treatment Options for Challenging Form of Epilepsy [press release]. Baltimore, MD: American Epilepsy Soceity; Published December 7, 2019. Accessed December 7, 2019.