WASHINGTON, DC – Add-on cannabidiol (CBD) for the treatment of Lennox-Gastaut syndrome (LGS) produces a clinically meaningful reduction in drop seizures regardless of whether patients are receiving concomitant clobazam or valproic acid, according to results presented at the 2017 American Epilepsy Society Annual Meeting, December 1-5, 2017 in Washington, DC.
The post-hoc analysis, led by Elizabeth A. Thiele, MD, PhD, of Massachusetts General Hospital in Boston, included nonrandomized subgroups from the GWPCARE3 (ClinicalTrials.gov Identifier: NCT02224560) and GWPCARE4 (ClinicalTrials.gov Identifier: NCT02224690) trials, which demonstrated safety and efficacy of add-on CDB for patients with treatment-resistant LGS. The study was prompted by a bidirectional pharmacokinetic interaction between CBD and clobazam observed in previous trials.
The current analysis included 396 patients who were previously randomly assigned to receive 10 mg/d CBD (n=73), 20 mg/d CBD (n=162), or placebo (n=161). Of the cohort, 194 patients were on clobazam and 202 were not.
During the 12-week maintenance period, 46% of patients who received 10 mg/d CBD plus concomitant clobazam experienced a ≥50% reduction in rates of drop seizures compared with 19% in the placebo group; similar responses were seen in patients who were receiving valproic acid (44% vs 10%). In addition, 33% of patients in the 10 mg/d CBD group who were off clobazam experienced a ≥50% reduction in rates of drop seizures compared with placebo; similar responses were seen in patients who were off valproic acid, as well (37% vs 15%).
Among the patients who received 20 mg/d CBD and were on concomitant clobazam, 57% experienced a ≥50% reduction in rates of drop seizures compared with 24% in the placebo group. Of those who were off clobazam, 35% experienced a ≥50% reduction in rates of drop seizures compared with 13% in the placebo group. Similar results were seen for those in the 20 mg/d CBD group who were both on and off valproic acid (47% vs 11%; 44% vs 23%). In patients with ≥37 weeks of follow-up, 58% and 57% of those who were on or off clobazam, respectively, experienced a ≥50% reduction in rates of drop seizures. The same results were seen for patients who were on or off valproic acid.
The researchers noted that somnolence was more prevalent in patients receiving CBD and clobazam compared with those who were off clobazam. Other adverse events in the treatment groups included decreased appetite, diarrhea, vomiting, constipation, pyrexia, and fatigue. Adverse events that led to treatment discontinuation in at least 1 patient in the CBD groups were increased levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase. The investigators noted, however, that most elevations resolved spontaneously and no patient met the standard criteria for drug-induced liver injury.
Disclosures: The study was funded by GW Research Ltd and Greenwich Biosciences. Drs Thiele and Devinsky have received financial support and honoraria from GW Pharmaceuticals; Daniel Checketts is an employee of GW Research Ltd; and Volker Knappertz is an employee of Greenwich Biosciences.
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Thiele EA, Devinsky O, Checketts D, Knappertz V. Cannabidiol treatment responder analysis in patients with Lennox-Gastaut syndrome on and off clobazam. Presented at: 2017 American Epilepsy Society Annual Meeting. December 1-5, 2017; Washington, DC.