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 study in Germany

Introduction: Lennox–Gastaut syndrome (LGS) and Dravet syndrome (DS) are rare and debilitating forms of epilepsy, characterised by recurrent, severe, drug-resistant seizures starting in infancy or early childhood, an increased risk of sudden unexpected death in epilepsy (SUDEP), and neurodevelopmental impairments. A non-psychotropic, plant-derived, highly purified formulation of cannabidiol (CBD; Epidyolex®, 100 mg/mL oral solution) has been approved in the EU for use in patients aged ≥2 years for the adjunctive treatment of seizures associated with LGS or DS in conjunction with clobazam (CLB), or for the adjunctive treatment of seizures associated with tuberous sclerosis complex. A retrospective, multicentre study was conducted to evaluate the real-world use of CBD oral solution in patients with drug-resistant epilepsies.

Methods: We performed a retrospective chart review of patients with drug-resistant epilepsies and treated with CBD at six epilepsy centres in Germany. We analysed patient and treatment characteristics, seizure outcomes, treatment retention rates (percentage of patients remaining on CBD treatment at time of assessment) and adverse events (AEs) for up to 12 months. Here, we present data for patients treated concomitantly with CBD and CLB.

Results: We identified 126 patients (102 LGS; 24 DS) 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 (Table 1). Patients were highly refractory to ASMs, with a median number of prior ASMs of 6 (range: 1–24), and concomitant ASMs of 3 (range: 1–7). During treatment with CBD+CLB, the most common concomitant ASMs were valproate (n=70, 55.6%), lamotrigine (n=38, 30.2%), brivaracetam (n=26, 20.6%), lacosamide (n=22, 17.5%), perampanel (n=22, 17.5%) and rufinamide (n=20, 15.9%). 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). A ≥50% reduction in total seizures was achieved by 47.5% of patients at 3 months (35.7–52.6% across age groups) and by 45.5% of patients at 12 months (44.4–46.2% across age groups) (Table 2). Of the patients who experienced generalized tonic-clonic seizures (GTCS) at baseline, a ≥50% reduction in GTCS was achieved by 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) (Table 2). Median seizure days per month significantly decreased from 30 (range: 0.5–30) to 15 (range: 0–30) in the 3-month period before and after CBD+CLB treatment (p<0.001). Treatment retention rates were 89.7%, 80.7% and 69.8% at 3, 6, and 12 months, respectively, and were similar across paediatric and adult groups (Table 2). Overall, 32 (25.4%) patients discontinued over the 12-month period, due to lack of treatment effectiveness (n=17, 13.5%), AEs (n=7, 5.6%), both treatment effectiveness and AEs (n=5, 4.0%) or other (n=3, 2.4%).

Conclusion: In patients with severe drug refractory LGS or DS, treatment with CBD+CLB demonstrated a reduction in seizure frequency and sustained treatment retention for up to 12 months across age groups in real-world clinical practice.