Director, Pediatric Neurology and Rehabilitation Medicine Texas Scottish Rite Hospital for Children Dallas, Texas
Rationale: Approximately 30%–60% of patients with TSC have a history of IS and are more likely to have treatment‑resistant epilepsy than those without IS. CBD was significantly superior to placebo in reducing seizures in children and adults with TSC in a Phase 3, randomized, placebo-controlled trial (GWPCARE6; NCT02544763). In this post hoc analysis of GWPCARE6, we compared response to CBD in patients with and without IS history. Methods: Eligible patients (1–65 yrs) had treatment-resistant epilepsy, ≥8 TSC-associated (countable focal and generalized) seizures during the four-week baseline, and were taking ≥1 antiseizure medication (ASM). Patients received plant-derived highly purified CBD (Epidiolex®; 100 mg/mL oral solution) at 25 mg/kg/d (CBD25) or 50 mg/kg/d (CBD50) or matched placebo for 16 wks. Efficacy of CBD vs. placebo was evaluated by percent reduction from baseline in TSC-associated seizure count in patients with and without IS history. Patients with documentation of current or prior infantile/epileptic spasms with onset age ≤2 yrs were categorized as having IS history. Negative binomial regression effect modification analysis was used to assess whether IS history affected CBD efficacy. Results: Of 224 patients enrolled, 138 (62%) had IS history. Median (range) age: 12.2 yrs (1.1–56.8) for patients with IS history and 10.5 yrs (1.6–55.8) for those without; 74% of patients in both groups were < 18 yrs. At baseline, patients with IS history were taking a median (range) of 3 (0–5) ASMs and had discontinued 4 (0–15); patients without IS history were taking 2 (1–5) and had discontinued 3 (0–13) ASMs. The median (Q1, Q3) monthly TSC-associated seizure frequency at baseline: 59 (28, 117) for patients with IS history and 51 (29, 96) for those without. CBD reduced TSC-associated seizures vs placebo regardless of IS history. For patients with IS history, percent reduction in seizure count from baseline was 45% for CBD25, 43% for CBD50, and 23% for placebo; placebo-adjusted reduction (95% CI) was 29% (6%–45%) for CBD25 and 25% (3%–43%) for CBD50. For patients without IS history, reduction was 54% for CBD25, 55% for CBD50, and 32% for placebo; placebo-adjusted reduction (95% CI) was 32% (5%–52%) for CBD25 and 34% (7%–54%) for CBD50. Effect modification analysis showed that treatment effect was comparable between patients with and without IS history (interaction p value, 0.803 for CBD25 and 0.561 for CBD50). AEs were reported by 93% of patients on CBD25, 100% on CBD50, and 95% on placebo; 8 patients (11%) on CBD25, ten (14%) on CBD50, and two (3%) on placebo discontinued treatment because of an AE. Most common AEs were diarrhea and somnolence, occurring more frequently with CBD than placebo. ALT/AST elevations ( >3× ULN) occurred in nine (12%) patients on CBD25, 19 (26%) on CBD50, and none on placebo; 79% of these patients were on concomitant valproate. Conclusions: CBD produced consistent reductions in TSC-associated seizures in patients with and without IS history. Funding: Please list any funding that was received in support of this abstract.: GW Research Ltd.