Abstracts

Rationale: Rufinamide (RFM) is a newer antiepileptic drug (AED) with a novel mechanism of action available in the U.S. since 2008. Existing post-marketing studies of RFM have either evaluated restricted populations (subjects originally enrolled in an RCT) or have short term follow up with outcome assessments made at varying time points between subjects. Retention rate is a useful observational measure of AED effectiveness because it combines efficacy and tolerability and reflects clinical practice. The aim of this study was to describe RFM use at a large pediatric epilepsy referral center in the first two years of its availability, using retention rate as the primary outcome measure. Methods: We conducted a single center retrospective cohort study. The electronic medical records of all patients seen at CHOP between 1/2009 and 12/2010 were searched for patients receiving at least one prescription for RFM in that time and having at least one follow up visit. Data were gathered by systematic manual chart review. The primary outcome measure was RFM failure, defined as discontinuation of RFM or initiation of an additional antiepileptic therapy. Kaplan-Meier methods curves were generated for time to RFM failure, for all patients and by reason for failure (efficacy versus tolerability). The impact of seizure type, fast or slow drug titration, and concomitant therapy with valproate on retention rate were evaluated using Cox regression models.Results: One hundred thirty five patients (65 female) were included for analysis, with 3 others excluded for lack of follow up and 2 excluded for not starting RFM after it was prescribed. Median age at seizure onset was 1 year (IQR 4 months to 3 years). Median age at RFM initiation was 10 years (IQR 6-15 years). Median time of follow up was 8.5 months (range 1 month to 27 months). The one year success rate was 43% and the 2 year success rate was 30%. RFM failure constituted discontinuation in 58(64%), and the remaining started additional treatment. Lack of efficacy was cited twice as often as lack of tolerability. Mechanism of seizure onset was generalized in 47, focal in 31, both focal and generalized in 45 and unknown in the rest. Syndrome diagnosis was Lennox Gastaut in 38, Infantile Spasms in 8, not identifiable in 67, with the remainder have other syndromes. At RFM initiation, patients were on a median 3 other AEDs (IQR 2-3), including valproate in 21. Concomitant valproate did not affect risk of RFM failure. Fast RFM titration (<2 weeks) was much more likely to result in RFM failure (HR 2.2, p=0.004). Presence of atonic seizures was associated with a 45% higher chance of RFM success (HR 0.55, p<0.01).Conclusions: Long term use of RFM without subsequent additional therapy occurred in 30%. RFM appears particularly effective for patients with atonic seizures. Though most drug failures were due to efficacy not tolerability, slower titration may result in a greater chance of RFM success.