2010
American Epilepsy Society Poster (Abst. 1.307)
The Safety and Efficacy of Vigabatrin for Pediatric and Adult Epilepsy in Community-Based Neurological Practice
Authors: Evan Fertig, S. Thompson, H. Husaini, S. Devi, G. Ghacibeh, M. Zaatreh, R. Kulikova, M. Lancman and D. McBrian
Rationale:
Vigabatrin (VGB) was recently FDA approved as monotherapy for pediatric patients with Infantile Spasms (IS) and as adjunctive therapy for adults with refractory complex partial seizures (CPS). Since VGB can cause up to a 30% risk of permanent visual loss, the FDA mandated a Risk Evaluation and Mitigation Strategy (REMS) to screen for Visual Field Deficits (VFDs). Transient MRI signal changes in subcortical areas mirroring intramyelinic edema seen in VGB-treated animals have also been observed, but the necessity of screening is unknown. Clinical data regarding VGB is primarily derived from academic centers with access to sophisticated ophthalmologic practice and neuroimaging. The goal of this study is to determine how its risks are addressed and its efficacy for a broad range of seizure types and epilepsy syndromes in community-based practice.
Methods:
Child/adult neurologists identified patients treated in the past 10 years with VGB, and chart review was performed using a standardized form.
Results:
The study included 7 children and 3 adults (50% F). Six/ten were treated for IS with the avg. age of seizure onset and VGB initiation of 6.8 mo/13.1 mo. One was treated with ACTH first; only one with VGB monotherapy. Avg. dose was 150 mg/kg/d (125-175 mg/kg/d); median therapy duration was 1 mo (1-108 mo). Etiologies included chromosomal defects-2, lissencephaly, cortical malformation, and cryptogenic-2. The avg. pre-treatment IS frequency/d was 10 (range 1-20); 2 also had CPS and 1 had subclinical seizures. Two were rendered seizure free (33%). One recently started and had an IS reduction from 20 to 1/d; data was not available for 1. One had a significant IS reduction (6-8/d to 1/wk) but with continued 1-2 GTC/wk; another had persistent IS with 0-3/d. Pre-/post-treatment EEG was available in 2 with resolution of all epileptiform activity in both. Post-treatment MRI was not performed. The remaining 4 were treated for LGS, TLE, TS, and unclassified. The median age of seizure onset and median age of VGB initiation was 10 mo/20 yrs. Avg. maintenance was 2.5 g/d with none seizure free or significantly improved. Overall, VFD screening was performed in all but 1 who has cortical blindness: 5 in academic centers, 3 in private, and 1 in an unknown. All had clinical/retinal exams, 4 ERGs, and 2 VFs. No treatment-induced VFDs were observed. Five/seven (71%) were thought to have benefitted and 6/7 (83%) would be treated again (3 missing answers).
Conclusions:
Initial results suggest that VGB was both safe and effective in community-based practice. For those treated for IS with known outcomes (n = 5), 40% were rendered seizure free and 80% had a significant reduction. Efficacy was not seen in the older group, possibly due to the relatively low doses used (2/3 of adults were on < 3 g/d). Ophthalmologic assessment was usually performed, with ERG in two-thirds of the children; VGB-related VFDs were not observed yet. MRI was not used to screen for signal changes, so their frequency cannot be stated. Future analysis will examine longer term efficacy and safety.