[P3.266] Comparison of Adverse Effects of USL255 and Commonly Prescribed AEDs: Assessment of Relative Risk
Kimford Meador,1Frank Gilliam,2Robert Hogan,3Mary Holmay,4Annie M. Clark,4Bob Anders4
1Stanford, CA, USA, 2Hershey, PA, USA, 3Saint Louis, MO, USA, 4Maple Grove, MN, USA
OBJECTIVE: To compare the adverse event (AE) profile of USL255, once-daily extended-release (XR) topiramate, with those of commonly prescribed immediate-release (IR) antiepileptic drugs (AEDs): lacosamide (LCM), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC) and topiramate IR (TPM-IR).
BACKGROUND: The goal of XR AEDs is to reduce dosing frequency and maintain constant plasma drug concentrations so that concentration-related adverse events are minimized. Once-daily USL255 is pharmacokinetically equivalent to twice-daily TPM-IR, but with reduced plasma fluctuations and peak dose concentrations.
DESIGN/METHODS: AEs reported in the Prescribing Information for LCM (200-400mg/day), LTG (up to 500mg/day), LEV (up to 3000mg/day), OXC (600-1200mg/day) and TPM-IR (200mg/day) were compared with those of USL255 (200mg/day) reported in a double-blind, phase 3 study (PREVAIL; NCT01142193). Risk ratios (RR) were calculated using methods described in the Cochrane Handbook for Systematic Reviews of Interventions (2005). To calculate RR for AEs with zero-cell counts, a continuity correction of 0.5 was used.
RESULTS: AEs with a particularly high risk compared to placebo (RR>10) were balance disorder (LCM, RR=29.6), speech disorder (LTG, RR=25.7), emotional lability (LEV, RR=18.1), arthralgia (LTG, RR=17.4), and weight decrease (USL255, RR=16.0). Somnolence, dizziness, and diplopia were the only AEs for which incidences were reported for all six drugs. Compared to placebo, all AEDs had a greater risk for somnolence (USL255, RR=6.0; LTG and OXC, RR=2.0; LEV, RR=1.9; TPM-IR, RR=1.7; LCM, RR=1.4) and dizziness (LCM, RR=3.1; LTG, RR=2.9; LEV, RR=2.3; OXC, RR=2.2; TPM-IR, RR=1.8; USL255, RR=1.2). All AEDs except USL255 had an increased risk for diplopia versus placebo (LCM, RR=4.5; OXC, RR=4.4; TPM-IR, RR=4.3; LTG, RR=4.0; LEV, RR=2.0 vs RR=0 for USL255).
CONCLUSIONS: These data suggest that USL255 has an overall favorable AE profile compared with commonly prescribed AEDs, but additional studies with head-to-head comparisons are needed to fully delineate differences in AE profiles.
Study Supported by: Upsher-Smith Laboratories, Inc.
Category - Epilepsy and Clinical Neurophysiology (EEG): Therapeutics: Medical
Tuesday, April 29, 2014 3:00 PM
P3: Poster Session III: Epilepsy and Clinical Neurophysiology: AED (3:00 PM-6:30 PM)