Markers of Bone Turnover and Lipid Metabolism During Eslicarbazepine Acetate (ESL) Monotherapy in Patients Taking or Not Taking Enzyme-Inducing Antiepileptic Drugs (EIAEDs) at Baseline (BL) (P2.030)

Objective: To evaluate the impact of ESL monotherapy on laboratory markers of bone turnover and lipid metabolism, and the effect of converting from an EIAED (carbamazepine or phenytoin) to ESL monotherapy. Background: AEDs, particularly EIAEDs, can cause changes in bone turnover and lipid metabolism leading to increased risk of osteoporosis and vascular disease. Methods: was an exploratory, post-hoc analysis of data from two Phase III ESL monotherapy trials (093-045;-046) and from an open-label extension study (OLE; -050). Patients (16-70 years; partial-onset seizures poorly controlled by 1-2 AEDs) received ESL 1600mg or 1200mg once daily (QD) for 16 weeks (10 weeks monotherapy) followed by OL ESL (800-2400mg) for up to 12 Laboratory markers of bone turnover and lipid metabolism were measured at BL, 18 weeks, and OL 12 months. Results: 365 patients took ≥1 ESL dose (1600mg or 1200mg QD); 130 (36[percnt]) took an EIAED at BL (+EIAED); and 235 (64[percnt]) did not (-EIAED). 180/274 patients who entered the OLE completed 1 year of treatment. At BL, most markers of bone turnover and lipid metabolism were higher in the +EIAED than -EIAED 18 weeks, changes in bone turnover markers were variable, but after 12 months, most markers were increased versus BL. At both time points, all lipid markers showed increases versus BL in the -EIAED group, but most markers showed reductions versus BL in the +EIAED group. Conclusions: After a year of OL ESL monotherapy, most markers of bone turnover were increased versus BL; the impact of BL EIAED use was variable. In -EIAED patients, all lipid markers increased during ESL monotherapy; in the +EIAED group, most showed reductions. This suggests an intermediate effect of ESL on these markers, consistent with a mild-to-moderate degree of enzyme induction.Study Supported by Sunovion Pharmaceuticals Inc. Disclosure: Dr. Constantino has received personal compensation for activities with Sunovion Pharmaceuticals Inc. Dr. Gidal has received personal compensation for activities with Upsher-Smith. Dr. Mintzer has received personal compensation for activities with UCB Pharma, Sunovion, Upsher-Smith Laboratories, Pfizer Inc., SK Pharmaceuticals, Vertex Pharmaceuticals, and Eisai Inc. as a speaker and/or consultant. Dr. Grinnell has received personal compensation for activities with Sunovion Pharmaceuticals. Dr. Blum has received personal compensation for activities with Sunovion Pharmaceuticals Inc. as an employee. Dr. Cheng has received personal compensation for activities with Sunovian Pharmaceuticals, Inc.