Long‐term efficacy and safety of cannabidiol in patients with tuberous sclerosis complex: 3‐year results from the cannabidiol expanded access program

Objective The cannabidiol (CBD) Expanded Access Program provided compassionate access to CBD for patients with treatment‐resistant epilepsy, including tuberous sclerosis complex (TSC), at 35 US epilepsy centers. Here, we present the long‐term efficacy and safety outcomes for add‐on CBD treatment in patients with TSC. Methods Patients received plant‐derived, highly purified CBD (Epidiolex® 100 mg/mL, oral solution), increasing from 2 to 10 mg/kg/d to tolerance or maximum of 25–50 mg/kg/d. Efficacy endpoints were percentage change from baseline in median monthly convulsive, focal, and total seizure frequency and ≥ 50%, ≥75%, and 100% responder rates across 12‐week visit windows through 144 weeks. Adverse events (AEs) are reported through 233 weeks. Results Thirty‐four patients with confirmed TSC were included. Mean age was 12.4 years (range, 1.8–31.2), and patients were receiving a median of 3 (range, 1–7) antiseizure medications (ASMs) at baseline. Median CBD dose was 25–28 mg/kg/d for 36 weeks and then 20–50 mg/kg/d through 228 weeks. Dose reduction from baseline occurred for most ASMs, except topiramate. Median reduction in the frequency of convulsive, focal, and total seizures was 44%–81%, 51%–87%, and 44%–87%, respectively, through 144 weeks. Responder rates (≥50%, ≥75%, and 100% reduction) were 43%–71%, 14%–58%, and 0%–25% for convulsive seizures; 52%–75%, 35%–60%, and 7%–32% for focal seizures; and 46%–79%, 26%–65%, and 0%–13% for total seizures. A total of 94% of patients experienced ≥1 AE; 47% had serious AEs, considered treatment unrelated by the investigator. Treatment‐related AEs (TRAEs) occurred in 71% of patients. The most frequently reported TRAEs were somnolence, diarrhea, and ataxia. Two patients experienced AEs leading to discontinuation. There were no deaths. Significance Long‐term add‐on CBD use was associated with reduced seizure frequency through 144 weeks. The safety profile was consistent with previous reports. Plain Language Summary In this study, we evaluated efficacy and safety of cannabidiol (CBD) treatment in patients with tuberous sclerosis complex receiving CBD in addition to other antiseizure treatments in an Expanded Access Program. After starting CBD, 46%–79% of patients had at least 50% reduction and 26%–65% had at least 75% reduction in the number of seizures per month; up to 13% had no seizures through 144 weeks. Safety results were similar to prior studies; sleepiness and diarrhea were common treatment‐related side effec