Real-world experience of cannabidiol in conjunction with clobazam for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome: Results from a retrospective multicentre chart review in Germany.

Background: Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) are rare and debilitating forms of epilepsy, characterised by recurrent, severe, drug-resistant seizures and neurodevelopmental impairments. A non-euphoric, plant-derived, highly purified formulation of cannabidiol (CBD; Epidyolex®, 100 mg/mL oral solution) is approved in the European Union and United Kingdom for use in patients aged ≥2 years for the adjunctive treatment of seizures associated with LGS or DS in conjunction with clobazam (CLB), and for the adjunctive treatment of seizures associated with tuberous sclerosis complex in patients aged ≥2 years.

Methods: We performed a retrospective chart review of patients with treatment-resistant epilepsies who were treated with adjunctive CBD at six epilepsy centres in Germany. We analysed patient and treatment characteristics, seizure outcomes, treatment retention rates (i.e. the proportion of patients remaining on CBD treatment at time of assessment and retention as estimated by Kaplan-Meier [KM] analyses), physician-rated Clinical Global Impression of Change (CGI-C), and adverse events (AEs) for up to 12 months. Here, we report data from this chart review for those patients with LGS or DS receiving adjunctive treatment with concomitant CBD and CLB.

Results: We identified 126 patients (102 LGS; 24 DS) receiving CBD and CLB, with a mean (standard deviation [SD]) age of 23.2 (15.8) years and a mean (SD) age of epilepsy onset of 3 (3.7) years. Patients had received a median (range) number of prior antiseizure medications (ASMs) of 6 (1-24) and concomitant ASMs of 3 (1-7). The median target CBD dose was 11.1 mg/kg/day in the total population (17.8, 15.8, and 9.7 mg/kg/day in the <6 years, 6-17 years, and ≥18 years subgroups, respectively). The median time to the target dose was 21-22 days across age groups. The median concomitant CLB dose was 0.14 mg/kg/day (0.38, 0.22, and 0.10 mg/kg/day in the respective age groups). A ≥50% reduction in total seizures was observed in 47.5% of patients at 3 months (35.7-52.6% across age groups) and 45.5% of patients at 12 months (44.4-46.2% across age groups). For generalised tonic-clonic seizures, a ≥50% reduction was observed in 63.0% of patients at 3 months (60.7-66.7% across age groups) and 56.9% of patients at 12 months (50.0-75.0% across age groups). Median seizure days per month significantly decreased from 30 (range: 0.5-30) at baseline to 15 (range: 0-30) at the last follow-up (p <0.001). Overall, 89.7%, 80.7%, and 69.8% patients remained on CBD at 3, 6, and 12 months, respectively. KM estimated treatment retention was similar across paediatric and adult groups, according to earlier or later initiation (e.g. ≤4 vs ≥15 prior and concomitant ASMs) and according to the syndrome (LGS and DS). Physicians rated 66% of patients demonstrated a CGI-C improvement and 67% demonstrated a CGI-C behaviour improvement. The most common AEs (≥5%) were sedation (n = 30, 23.8%), diarrhoea (n = 13, 10.3%) and psycho-behavioural AEs (n = 9, 7.1%).

Conclusion: In this chart review of patients with severe treatment refractory LGS or DS receiving adjunctive CBD and CLB concomitantly, a reduction in seizure frequency and sustained treatment retention was observed for up to 12 months across age groups in real-world clinical practice. CBD discontinuations exclusively due to AEs were infrequent and the AE profile was generally aligned to that previously observed.