Abstracts

Rationale: Cannabidiol (CBD) has shown promise as an antiepileptic agent in various open-label studies. The goal of this study is to assess seizure response to pharmaceutical grade CBD (Epidiolex) in children and adults with video-EEG confirmed treatment-refractory epilepsy who have failed at least 4 different AEDs, and who were experiencing on average at least 4 countable seizures per month prior to enrollment (simple partial seizures without motor component were excluded), and to develop a predictive dose-response relationship. Methods: In 81 patients (42 children; 39 adults), pre-CBD seizure frequency was averaged over 3 months prior to initiating CBD at 5mg/kg/day for seizure control with flexible adjustments as tolerated q2 weeks by 5mg/kg/day up to a maximum of 50mg/kg/day. Bi-weekly seizure frequency was monitored via diary that was reviewed with patient/caregiver at each visit. Other AEDs were adjusted as needed (especially clobazam and valproate). The six response models tested were 3- and 6-months follow-up times for all patients and 3- and 6-months follow-up times for pediatric and adult patients. The CBD dose ?" seizure response relationship was identified by matching the seizure response to dose used after controlling for the baseline seizure frequency. Standard statistical measures were used for this non-normally distributed cohort. Results: The 3- and 6-month models for all patients were significant (p=0.007 and p=0.002, respectively) with the most optimal dose of CBD at 3 months being ~20mg/kg/day and ~25mg/kg/day at 6 months (corresponding models are y=87.1265 + 0.3595z - 10.2575x + 0.2608x^2 and y=76.5542 + 0.3313z ?" 6.7769x + 0.1325x^2, respectively). For pediatric patients, the 3- and 6-month models were also significant (p=0.03 and p=0.004, respectively) with the most optimal dose being ~20mg/kg/day for both time points (corresponding models are y=140.4 + 0.3529z ?" 17.4873x + 0.4480x^2 and y=127.98 + 0.3272z ?" 13.4383x + 0.2988x^2, respectively). The 3- and 6-month models for adults were trending towards significance at 3 (p=0.15) but not at 6-months (p=0.687). Of all patients, at 2 consecutive visits 55/81 (68%) had >25% reduction in seizure frequency, 47/81 (58%) had >50% reduction in seizure frequency, 29/81 (36%) had >75% reduction in seizure frequency, and 7/81 (9%) were seizure free. These responder rates for pediatric and adult groups are 69% and 74% (>25% reduction, respectively), 59% and 56% (>50% reduction), 38% and 33% (>75% reduction), and 13% and 2% (seizure-free). Conclusions: This compassionate use open-label study indicates the anti-seizure effects are observed early in the treatment process with the modelling indicating the most optimal dose response between 20 and 25mg/kg/day. While the responder rates are similar between children and adults, non-significant results observed in adults are likely related to much higher variability in response to CBD. Funding: State of Alabama