Authors :
Michal Tzadok, MD – Pediatric Neurology Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Rotem Pollack, Ph.D – Neopharm Israel, Petch Tikva, Israel; Hadar Florh, MD – Pediatric Neurology & Development Center, Shamir Medical Center (Assaf Harofe), Zerifin, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Yael Yosef Michael, MD – Pediatric Neurology Unit, Wolfson Medical Center, Holon, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Tal Gilboa, MD – Pediatric neurology unit, Hadassah university hospital, Jerusalem, Israel; Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel; Bruria Ben Zeev, MD – Pediatric Neurology Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Shimrit Uliel-Sibony, MD – Pediatric Neurology Institute, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
This is a Late Breaking abstractRationale: Approximately 30% of childhood epilepsy cases are resistant to drugs. In addition to the risks of seizures and the consequences of multiple anti-epileptic therapies, drug-resistant epilepsy (DRE) significantly affects the development of children and their quality of life. Epidiolex
® 100 mg/mL oral solution (
Jazz Pharmaceuticals, Cambridge, UK), a plant-derived, purified CBD, was approved by the Israeli Ministry of Health as an add-on therapy for adults and children ≥2 years with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) and for patients >1 year with tuberous sclerosis complex (TSC) syndrome. (Epidiolex is approved in other countries, please see the relevant country product information for details). The current study aims to describe the safety and efficacy of purified CBD in a real-life circumstance.
Methods: A retrospective analysis of the efficacy and safety of purified CBD in children and young adults with DRE treated from 2018 to 2022 at 5 medical centers in Israel.
Results: A total of 139 children and young adults (54.7% female, median age 12.0 years [range, 2.3-29.2]) were treated with purified CBD. The most common etiology was LGS (37.4% of patients) followed by DS (16.5%) and TSC (16.5%). Median purified CBD dose was 12.5 mg/kg (range, 2.5-20.0) and median treatment duration was 9.0 months (range, 0.5-48.0). Most patients (85.6%) experienced a reduction in seizure frequency following initiation of treatment; 38.8% had more than 50% reduction. Fifty-three patients (38.1%) had positive side effects: 44 (31.7%) showed improved alertness, 14 (10.1%) had improved speech and 3 (2.2%) achieved new developmental milestones. A multivariate linear model for assessment of predictive factors for seizure reduction demonstrated that patients who had more than 50% reduction in seizure frequency during prior treatment with CBD oils, were also more likely to have a reduced frequency of seizures while they were treated with purified CBD (p < 0.0001). Development, etiology, age, purified CBD dose (0-10 mg/kg vs. 10-20 mg/kg) and concomitant treatment with clobazam, valproic acid or everolimus had no effect on the efficacy of purified CBD on seizure reduction. Thirty-nine patients (28.1%) experienced at least one adverse event (AE). The most common AEs were irritability (20.9%) and drowsiness (12.9%). Forty-two patients (30.2%) discontinued treatment due to lack of efficacy (16.5%), seizure aggravation (5.8%), intolerance (3.6%), and AEs (3.6%). Among the 23 patients for whom treatment with purified CBD did not show efficacy, the median duration of treatment was 6 months (95% CI, 3-8).