Abstracts

Rationale: Rufinamide (RUF), a triazole derivative, is a new-generation anti-seizure medication (ASM) with a novel mechanism of action. RUF was first FDA-approved in 2008 for adjunctive treatment of seizures associated with Lennox-Gestaut syndrome in patients 4 years and older, and expanded in 2015 to include patients 1 year of age and older. Information on the experience using this medication in the pediatric population less than 4 years of age in the US remains limited. We evaluated the efficacy and safety of RUF treatment in pediatric epilepsy patients under 4 years of age at our center. Methods: Children under 4 years of age with pharmacologically intractable epilepsy, who were treated with RUF at Boston Children’s Hospital between 2010 and 2018 were included in this retrospective study. Variables including demographics, RUF administration information, adverse effects, and Seizure Frequency (SF) were obtained from medical records utilizing a standard data acquisition tool. Efficacy was evaluated based on the reduction of seizure frequency. Safety and efficacy of RUF treatment were assessed at two time intervals: immediately prior to initiation of RUF, and at the last follow-up visit. Baseline SF was defined as SF at the one month period of time before initiation of RUF, and seizure frequency was subsequently assessed as seizure count per month. Response to treatment was defined as greater than 50% reduction in seizure frequency upon follow-up as compared to baseline. Patients with missing information were excluded from the analysis. Results: We reviewed records of 128 children under 4 years who received RUF, and included 103 with complete information. Patients consisted of 60 males (58%), with a median age of 20 (IQR; 13-28, range 2-36) months. Median treatment duration was 15 months, and median RUF dosage at the last follow-up was 42 (IQR; 34-56) mg/kg. Epilepsy types were categorized as generalized (81, 78.6%), focal (7, 96.8%), and combined (15, 14.6%). At the last follow-up visit, there was a significant seizure reduction (450 vs 90, p<0.001). Fifty-one patients (49.5%) responded to the treatment, including 20 (19.4%) who achieved seizure freedom. All 5 patients with Lennox-Gestaut Syndrome responded to RUF. Thirty patients (29%) developed adverse reactions (ARs) during RUF treatment; the most common ARs were somnolence (12, 11.6%), irritability (10, 9.7%), nausea (7, 6.7%), and sleep problem (5, 4.8%). 41 patients (39.8%) discontinued RUF due to adverse effects (15, 14.5%) or lack of efficacy (26, 25.2%). Conclusions: RUF was effective in reducing seizure frequency in pediatric epilepsy patients under 4 years of age, and was overall tolerated well. Adverse effects lead to RUF treatment discontinuation in 14% of patients. Funding: This study was funded by an investigator initiated grant by Eisai Inc.