Abstracts

Rationale: Rufinamide (RFM) was licensed for use in the treatment of Lennox-Gastaut Syndrome (LGS) in 2008. The present chart review was conducted to assess the safety, efficacy, and retention when rufinamide is used off-label in adults with refractory epilepsy other than LGS, and to compare to on-label use.Methods: We conducted a retrospective chart review of the first 48 adult outpatients prescribed RFM at the Columbia University Comprehensive Epilepsy Center. This project is part of the Columbia AED Database, which funded by several pharmaceutical companies, including Eisai, the distributer of rufinamide.Results: The mean was age 41, ranging from 18 to 70 years. Patients consisted of 13 (27%) with Symptomatic Generalized Epilepsy, including 6 LGS, 20 (42%) with Primary Generalized Epilepsy (PGEN), 13 (27%) Focal Epilepsy, and 2 (4%) Focal and PGEN. We looked at drug retention at six and twelve month time periods, where retention was defined as the number of patients on RFM for the time period or greater, out of the total number of patients, excluding those on the drug for less than the time period and still on it. At six months, 30 (71%) patients remained on RFM and at twelvemonths, 9 (29%) remained. On-label patients had retentions of 4/6 and 1/3, with off-label patients showing similar retentions of 26/36 (72%) and 8/28 (27%) for six and twelve months, respectively. 16 (33%) patients reached the recommended dose of 3200mg or higher. 17 (35%) experienced adverse effects attributed to RFM that led to dose change or discontinuation. Dizziness (6.3%) and GI upset (6.3%) were the most common side effects. In the 38 patients with documented seizure frequencies, 8 (21%) experienced a 50% or greater decrease in seizure frequency (responders). Among responders, improvement occurred most often at 1600mg/day (4 patients), with maximum dose at 3200mg/day (3), and final dose at 1600mg/day (4). Of the 6 LGS patients, 1was a responder. 7 of the 32 (22%) off-label patients were responders. Seizure worsening (>50% increase in seizure frequency) while on RFM (often while tapering off another AED) occurred during on-label use in 1/6 cases, and during off-label use in 10/32 patients. All seizure types seem to respond similarly, though numbers were very small for this analysis.Conclusions: The results of this study indicate that rufinamide can be a useful adjunctive agent for adult patients with refractory epilepsy, both on- and off-label, regardless of epilepsy syndrome. Total retention on RFM was high at six months (71%), dropping considerably by 12 months (29%). Only a third of patients reached the maximum recommended dose, with maximum benefit most commonly seen at 1600 mg/day. Adverse effects were mild, transient, and consistent with previous studies. Further studies are needed to determine the best candidates for RFM, but rufinamide appears to be effective in some patients with a variety of epilepsy syndromes.