Children treated with cannabidiol to control seizures caused by Lennox Gastaut syndrome (LGS) benefited from the therapy for at least three years, researchers reported at the 2020 virtual conjoint meeting of the Child Neurology Society and International Child Neurology Association.
After 156 weeks of treatment, the median percentage of reduced drop seizures in 12-week windows were 48 percent to 71 percent and 48 percent to 68 percent for total seizures, said Anup D. Patel, MD, FAAN, section chief of neurology and associate professor of clinical pediatrics at Nationwide Children's/Ohio State University in Columbus.
“Long-term treatment with add-on cannabidiol in patients with LGS produced sustained seizure reductions with no new safety concerns," Dr. Patel stated in his presentation of the data.
Participants in the open-label extension study were gleaned from two phase 3, randomized, controlled clinical trials, known as GWPCARES3 and GWPCARES4. They included 366 patients who had been diagnosed with LGS, a rare and severe childhood-onset epilepsy, characterized by multiple and concurrent seizure types, cognitive dysfunction, and slow spike waves on EEG. The mortality of the syndrome is 5 percent in childhood, and seizures may persist into adulthood in more than 80 percent of patients.
In the open-label extension trial, 99 percent of the patients in the controlled clinical trials were treated with plant-derived, highly purified cannabidiol (100 mg/mL oral solution of Epidiolex). The mean age of the patients was 16 years of age and 54 percent were boys. At baseline, the median drop seizure frequency over 28 days was 80 seizures; the median total seizures was 168 events in 28 days.
After a median follow-up of 150 weeks, Dr. Patel reported that 113 participants dropped out of the study—about 33 percent of the original patient population. Overall, 96 percent of the patients in the studies reported adverse events, including diarrhea, pyrexia, vomiting, upper respiratory tract infection, and decreased appetite. Forty-two percent of the adverse events were considered serious, which led to discontinuing the therapy in 12 percent, the researchers reported in their abstract. There were 11 deaths during the study, but the investigators did not find that any of those deaths were related to their treatment.
The study was supported by GW Research Ltd.
Commenting on the study, Fred A. Lado, MD, PhD, Northwell Health's regional director of epilepsy for Queens and Great Neck, NY, said, “LGS is one of the conditions with an FDA indication for use of cannabidiol. While this study validates the benefits of cannabidiol, it also provides an important perspective that cannabidiol—like other seizure medications—is associated with adverse effects, including liver function abnormalities in 8 percent.
“There is still an impression among the lay public that cannabidiol, being derived from the hemp plant, is a more 'natural' molecule than antiseizure medications developed in the laboratory," Dr. Lado told Neurology Today At the Meetings. “These data show that the incidence of serious adverse effects may be high—42 percent—leading to discontinuation of cannabidiol in 12 percent of the study participants."
“Hopefully these data will enable neurologists to help patients to understand that like other antiseizure medications, cannabidiol may be of sustained benefit in seizure control, but the risk of adverse effects must be taken into consideration as well," he said.
Dr. Patel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Greenwich Biosciences and Medscape. Dr. Patel has received research support from GW Research Ltd. Dr. Lado did not disclose any relationships with industry.
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CNS-ICNA PL12: Patel A, Gil-Nagel A, Chin R, et al. Long-term safety and efficacy of cannabidiol (CBD) treatment in patients with Lennox Gastaut syndrome (LGS): 3-year results of an open-label extension (OLE) Trial (GWPCARE5).