Comprehensive postmarketing review of visual defects reported with topiramate (P6.032)

OBJECTIVE: To determine possible mechanisms of action (MOA) for visual field defects (VFDs), and patterns for development of VFDs with topiramate treatment. BACKGROUND: Treatment-emergent adverse events (TEAEs) including VFDs reported with topiramate use, are usually reported as reversible. DESIGN/METHODS: A comprehensive topiramate database review included: 1) preclinical data - to evaluate topiramate’s MOA compared with other antiepileptic drugs (AEDs) associated with VFDs, and 2) sponsor’s clinical trials database, postmarketing spontaneous reports, and medical literature. All TEAEs suggestive of retinal dysfunction or damage were summarized by system and organ class (SOC) and preferred term (MedDRA version 14.0). A relative risk (RR) analysis was conducted using data from topiramate double-blind, placebo-controlled trials (DBPCTs). RESULTS: Topiramate-treated patients showed greater frequency of TEAEs suggestive of retinal dysfunction or damage versus placebo-treated (0.3[percnt]-0.7[percnt] vs. ≤0.1[percnt]) patients in DBPCTs for approved indications; similar incidence was noted in open-labels (OLs) and in DBPCTs for investigational indications. In OLs (each investigational indications), incidence was <0.1[percnt] (except diabetic peripheral neuropathy [1.4[percnt]]). 88[percnt] of TEAEs were mild-moderate. Serious events were rare, and most were not treatment limiting and resolved. Most common visual TEAEs were VFD, scotoma and optic atrophy (approved indication trials), and VFD, tunnel vision, retinopathy, retinal hemorrhage and retinal detachment (investigational indication trials). Incidence of TEAEs in DBPCTs (approved and investigational indications) was higher in topiramate-treated (N=9169) versus placebo-treated patients (N=5023) (0.36[percnt] vs. 0.24[percnt]), RR to placebo-treated patients was 1.5 (95[percnt] CI, 0.776-2.898); not statistically significant. CONCLUSIONS: As VFD is not a common TEAE with other AEDs that have a gamma-aminobutyric acid-ergic MOA similar to topiramate; therefore, retinal function is not a class effect. A comprehensive review of topiramate data revealed an increased incidence of visual TEAEs in topiramate-treated versus placebo-treated patients, however, RR was not statistically significant. Topiramate prescribing information includes warnings related to visual TEAEs. Disclosure: Dr. Ford has received personal compensation for activities with Johnson and Johnson as an employee. Dr. Jeffrey has received personal compensation for activities with Janssen Pharamceuticals, Allergan, Inc., and Theravance Biopharma. Dr. Selan has received personal compensation for activities with Janssen Pharmaceutica. Dr. Greenberg has received personal compensation for activities with Janssen Pharmaceuticals, Inc. Dr. Shi has received personal compensation for activities with Janssen.