Abstracts

Rationale: The key safety issue for vigabatrin (VGB) is risk of vision loss. To manage this risk, the FDA and Lundbeck require a comprehensive Risk Evaluation and Mitigation Strategy (REMS), including an ongoing patient registry, designed to ensure regular vision monitoring, facilitate ongoing benefit-risk assessments, and detect VGB-associated peripheral visual field deficits as early as possible.Methods: Registry participation is mandatory for all US VGB prescribers and patients (pts). Basic registry methodology has been published.¹ Ophthalmologic assessments are required at baseline, every 3 months during therapy, and 3 6 months post-discontinuation. Current analyses cover the 4-year period from Aug. 21, 2009, through Aug. 27, 2013. Two independent expert neuro-ophthalmologists (masked to pts identities), members of the Sabril Registry steering committee, evaluated voluntarily submitted, detailed vision test findings from a subset of pts for technical adequacy and clinical significance.Results: As of Aug. 27, 2013, 5,487 pts were enrolled, of which 3,436 had infantile spasms (IS), 1,696 had refractory complex partial seizures (rCPS), and 343 had other diagnoses. Median duration of VGB treatment in the registry was 9.9 months (range: 0.1 to 47.1 months). Total exposure to VGB is unknown, because some pts entered after having received VGB from other sources. 3,242/5,487 (59%) had discontinued VGB after enrolling in the registry, and 15/3,242 (0.5%) discontinued because of reported visual field deficits. A total of 399/5,487 pts underwent perimetry, and approximately 10% of those eligible for vision testing at subsequent time points completed perimetry. 11 pts with rCPS continuing on therapy met predefined REMS criteria for vision loss, based on changes in visual acuity. A separate data subset of 928 pts with cumulative detailed vision results (i.e., all those for whom vision results were voluntarily submitted) was reviewed by the neuro-ophthalmologists. 23% of all those tests showed clinically significant existing pathology assessed as unrelated to VGB, regardless of prior exposure to VGB at registry entry. The most common pre-existing deficits included visual field loss, optic disc pallor, or abnormal electrophysiology, all a reflection of the effects of underlying conditions and prior therapies (e.g., neurosurgery) on vision. 24 pts (2.6% of 928 pts with voluntarily submitted results) were found to have a vision effect possibly or probably related to VGB.Conclusions: Through a subset of 928 pts with voluntarily submitted vision test results, the Sabril Registry continues to detect afferent visual system abnormalities at baseline for >20% of pts with IS, rCPS, or other epileptic conditions. Median exposure at this time is approaching 1 year. 15/3,242 (0.5%) pts to date have discontinued because of reported visual field deficits, and 24/928 (2.6%) of those with voluntarily submitted vision results were determined to have had a vision deficit possibly or probably related to VGB. 1Pellock JM, et al. Epilepsy Behav. 2011;22:710 7.