Long-term efficacy and safety of cannabidiol (CBD) in children with treatment-resistant epilepsy: Results from a state-based expanded access program.
Epilepsy Behav
; 112: 107474, 2020 11.
Article
en En
| MEDLINE
| ID: mdl-33181893
ABSTRACT
INTRODUCTION:
An intermediate-sized, multicenter, expanded-access study was opened in 2015 through the support of the State of Georgia. This study provided children with treatment-resistant epilepsy (TRE) access to plant-derived highly purified cannabidiol (CBD; Epidiolex® in the US; Epidyolex® in the EU; 100â¯mg/mL oral solution). These children had failed to achieve seizure freedom with available treatment options and were ineligible to participate in randomized controlled trials that only included patients with Lennox-Gastaut and Dravet syndromes.METHODS:
Cannabidiol safety, changes in seizure type, frequency, and seizure-free days were evaluated for children aged 1-18â¯years (at time of consent) as an adjunctive treatment for 36â¯months. The study consisted of a two-month baseline period, a titration period, treatment period, and optional titration period, which occurred after ≥26â¯weeks of treatment. Cannabidiol treatment was administered up to a targeted dose of 25â¯mg/kg/day, with an optional secondary treatment up to 50â¯mg/kg/day. Daily seizure type, seizure frequency, and seizure-free days were recorded in a Web-based diary, and changes in these outcomes were recorded and analyzed for the duration of the study. The occurrence of adverse events (AEs) was also recorded.RESULTS:
The median percentage change in seizures for 45 patients in Months 3, 6, 12, 18, 24, and 36 showed a statistically significant (pâ¯<â¯0.001) reduction in major seizures (ranging from 54 to 72% at various time points) and all seizures (61-70%) compared with baseline. A mean increase in seizure-free days per 28â¯days was >5 in all treatment periods after Month 2, and an average increase of 7.52 (pâ¯<â¯0.001) seizure-free days per 28â¯days was observed at the end of follow-up compared with baseline. All patients experienced ≥1 AE. Children who transitioned to the optional secondary treatment (high-dose group) reported more AEs before increasing their dose to >25.0â¯mg/kg/day compared with the low-dose group. However, the average rate of AEs was significantly lower after moving to a high-dose regimen (pâ¯=â¯0.004). Twelve children reported 20 serious AEs, none of which were considered related to CBD.CONCLUSIONS:
This study supports CBD as an adjunctive treatment for children with TRE. Treatment was well tolerated in doses up to 50â¯mg/kg/day. Patients who did not achieve desired results at a dose of ≤25.0â¯mg/kg/day reported more AEs when CBD dose increased to >25.0â¯mg/kg/day. Decreases in major seizure frequency and an increase in seizure-free days compared with baseline were reported during treatment. This supports the efficacy and tolerability of CBD for mixed seizure etiologies.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cannabidiol
/
Epilepsias Mioclónicas
/
Epilepsia
Tipo de estudio:
Clinical_trials
Límite:
Adolescent
/
Child
/
Child, preschool
/
Humans
/
Infant
Idioma:
En
Revista:
Epilepsy Behav
Asunto de la revista:
CIENCIAS DO COMPORTAMENTO
/
NEUROLOGIA
Año:
2020
Tipo del documento:
Article