Add-on cannabidiol in patients with Dravet syndrome: Results of a long-term open-label extension trial
Objective: Add-on cannabidiol (CBD) reduced seizures associated with Dravet syndrome (DS) in two randomized, double-blind, placebo-controlled trials: GWPCARE1 Part B (NCT02091375) and GWPCARE2 (NCT02224703). Patients whocompletedGWPCARE1 PartA(NCT02091206)orPartB,orGWPCARE2,were enrolled in a long-t...
| Autores: | , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/68905 |
| Acceso en línea: | https://hdl.handle.net/10171/68905 |
| Access Level: | acceso abierto |
| Palabra clave: | Antiseizure medication Cannabinoid Childhood onset epilepsy Convulsive seizures Dravet syndrome |
| Sumario: | Objective: Add-on cannabidiol (CBD) reduced seizures associated with Dravet syndrome (DS) in two randomized, double-blind, placebo-controlled trials: GWPCARE1 Part B (NCT02091375) and GWPCARE2 (NCT02224703). Patients whocompletedGWPCARE1 PartA(NCT02091206)orPartB,orGWPCARE2,were enrolled in a long-term open-label extension trial, GWPCARE5 (NCT02224573). We present an interim analysis of the safety, efficacy, and patient-reported outcomes from GWPCARE5. Methods: Patientsreceived a pharmaceutical formulation of highly purified CBD in oral solution (100 mg/ml), titrated from 2.5 to 20 mg/kg/day over a 2-week period, added to their existing medications. Based on response and tolerance, CBD could be reduced or increased to 30 mg/kg/day. Results: Of the 330 patients who completed the original randomized trials, 315 (95%) enrolled in this open-label extension. Median treatment duration was 444 days (range = 18–1535), with a mean modal dose of 22 mg/kg/day; patients received a median of three concomitant antiseizure medications. Adverse events (AEs)occurredin97%patients(mild,23%;moderate,50%;severe,25%).Commonly reported AEs were diarrhea (43%), pyrexia (39%), decreased appetite (31%), and somnolence (28%). Twenty-eight (9%) patients discontinued due to AEs. Sixtynine (22%) patients had liver transaminase elevations >3 × upper limit of normal; 84% were on concomitant valproic acid. In patients from GWPCARE1 Part B and GWPCARE2, the median reduction from baseline in monthly seizure frequency assessed in 12-week periods up to Week 156 was 45%–74% for convulsive seizures and 49%–84% for total seizures. Across all visit windows, ≥83% patients/caregivers completing a Subject/Caregiver Global Impression of Change scale reported improvement in overall condition. Significance: We show that long-term CBD treatment had an acceptable safety profile and led to sustained, clinically meaningful reductionsin seizure frequency in patients with treatment-resistant DS. |
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