To assess changes in seizure frequency (SF) and severity (Chalfont Seizure Severity Scale; CSSS) and durability of the response to CBD (Epidiolex®) in patients with treatment-refractory epilepsy enrolled in an open-label compassionate use safety study.
Patients with video-EEG confirmed epilepsy who have failed at least 4 different AEDs and were experiencing on average ≥4 countable seizures per month were enrolled.
In 132 patients (70 pediatric) pre-CBD SF and CSSS were averaged over 3 months prior to initiating CBD at 5mg/kg/day; dose increases were made as tolerated q2 weeks by 5mg/kg/day up to a maximum of 50mg/kg/day. SF and CSSS were collected at 12, 24, and 48 weeks after enrollment. Other AEDs were adjusted as needed. Standard statistical measures including censoring for dropouts and early terminations were used for this non-normally distributed cohort.
At the time of the analyses, of the 132 enrolled patients, 130 had 12 week, 88 had 24 week, and 61 had 48 week data (411 individual encounters). There were no differences between participants who contributed all 4 data points and who contributed less than 4 data points (<4 data points were either due to dropping out or not being in the study for long enough) in basic demographic and seizure variables. For the entire group, bi-weekly SF decreased from mean of 144.4 at entry to 52.2 at 12 weeks (p<0.001), 66.6 at 24 weeks, and 46.7 at 48 weeks (differences between 12, 24, and 48 weeks NS). CSSS numbers were 80.7 (p<0.001), 39.26, 40.72, and 34.6 respectively (differences between 12, 24, and 48 weeks NS). Data split between pediatric and adult groups mimicked the same response pattern.
This compassionate use open-label study indicates significant improvements in SF and CSSS at 12 weeks with response maintained over the 48-week duration of the study.
Study supported by: State of Alabama
"Pharmaceutical-grade cannabidiol improves seizure frequency in children and adults, and also decreases their severity," Jerzy P Szaflarski, MD, PhD, professor and director of the UAB Epilepsy Center in Birmingham, Alabama, told Medscape Medical News.
"There was a dramatic seizure decrease in children, driven mainly by the patients with very high seizure frequencies," he added...
Pediatric patients tended to experience generalized seizures, whereas adults reported mainly partial or focal-onset seizures, "which may explain some of the differences we see." The accuracy of seizure counts in diaries prepared by patients and families was another potential limitation...
Going forward, Szaflarski would like to determine whether cannabidiol, in combination with other cannabinoids such as tetrahydrocannabinol, is more efficacious than cannabidiol alone. He also would like to assess other cannabinoids that might have efficacy in seizure control. "We need to determine the effects of cannabidiol on the central nervous system, neuroimaging, cognition [and more]," he added.
Commenting on the findings for Medscape Medical News, Gregory D Cascino, MD, Whitney MacMillion Jr professor of neuroscience at the Mayo Clinic College of Medicine, enterprise director of epilepsy for the Mayo Clinic (both in Rochester, Minnesota), and a fellow of the AAN, said it is "an important study."
"They looked at a composition of patients like those that we see in the real clinical practice setting — adults and pediatric patients. They also had patients who were refractory to four or more antiepileptic drugs, so [the patients] clearly had drug-resistant epilepsy," he said
"This is a well-done, open-label study," Cascino added. "What I found was helpful is there was benefit at 12 weeks, a sustained benefit as they followed patients out several months."
"As with many of the drug investigation studies, there was a moderate reduction in seizure tendency. It certainly compares very favorably to patients who are enrolled in adjunctive antiepileptic drug trials."