Abstracts

Rationale: Clobazam has been approved in the United States by the FDA as an adjunctive therapy for the treatment of seizures associated with Lennox-Gastaut syndrome in patients 2 years of age and older. However, information on the experience using this medication in the pediatric population in the US is extremely limited. We aim to describe our experience with the efficacy and safety of clobazam in refractory epilepsy in a large population of children less than two years of age. Methods: We retrospectively reviewed all patients between 0 and 2 years of age at Boston Children’s Hospital from October 2011 to December 2016. We included patients who were treated with clobazam for refractory epilepsy, and who had a follow-up visit at least one month after starting clobazam. Response to clobazam was defined as >50% reduction in seizure frequency at the time of last follow-up visit as compared to baseline.  Results: One-hundred-and-fifty-five patients received clobazam, of which 116 [median age 12 months, IQR (p25-p75) 8-16 months] had full follow-up data ≥1 month after starting clobazam. Median follow-up age was 14 months [IQR (p25-p75) 9-18 months]. At the time of clobazam initiation, 31/116 (27 %) patients were on one antiepileptic drug (AED), 52/116 (45%) patients were on two AEDs, and 26/116 (22%) patients were on 3 or more AEDs. 7/116 (6%) patients received clobazam monotherapy. Overall response rate was 33% (38/116) with a median seizure reduction of 75%. 18 (16%) patients had ≤50% reduction, 14 (12%) had no change and 16 (14%) had worsening of seizure frequency. 30 (26%) patients became seizure free. Both epileptic spasms and focal seizure types, as well as structural metabolic and unknown etiologies, showed reduction in seizure frequency (Table 1). The median (IQR) starting dose was 0.42 (0.25 - 0.655) mg/kg/day, increasing 2.5 (1-5) mg/week to an initial titration target dose of 7.5 (5-10) mg/day. 8 (7%) patients discontinued clobazam, 5 (4%) due to adverse effects and 3 (3%) due to lack of efficacy. The most common adverse effects were feeling weak, tired or irritable in 13 patients (11%) followed by drowsiness, dizziness reported in 3 patients (3%).  Conclusions: Clobazam is both well tolerated and effective in reducing seizure frequency in pediatric patients less than two years of age with refractory epilepsy. Efficacy was observed across a variety of etiologies and seizure types. Funding: This study was funded by Lundbeck.