Abstracts

Rationale: Vigabatrin (VGB) was licensed in the UK as an antiepileptic drug (AED) in 1989 and has been used throughout Europe. Reports of vision changes following exposure to VGB were first published in 1997. Approved in the US in 2009, VGB (Sabril^®) is currently indicated as adjunctive therapy for refractory Complex Partial seizures (rCPS) in patients ≥10 years who have responded inadequately to several alternative treatments, and as monotherapy for Infantile Spasms (IS) in patients 1 month to 2 years of age. As part of the FDA-mandated risk evaluation mitigation strategy (REMS) program, the Sabril^® Registry monitors patients to help detect and describe VGB-associated vision loss and to capture demographic and clinical characteristics of US Sabril^® patients. Methods: Registry participation is mandatory for all US Sabril^® prescribers and patients. A benefit-risk assessment must be documented by the physician for a patient to progress to maintenance therapy, defined as 1 month of VGB treatment for IS patients and 3 months for rCPS patients. Ophthalmologic assessments must be documented during and after completion of therapy. To meet predetermined criteria for visual acuity or visual field loss, a reduction in vision relative to baseline during two consecutive vision assessments using consistent methods must be demonstrated. Results: Of the 6,823 registry patients, 2,055 had rCPS, 4,309 had IS, and 442 had other diagnoses. A total of 5,546 were <17 years, and 1,200 were ≥17 years. At enrollment, 81% of patients <17 years and 86% of patients ≥17 years were VGB-naïve. Most pediatric patients attempted ≤3 treatments (including ACTH/steroids for IS) prior to VGB, and the majority were taking 1-3 AEDs upon VGB initiation. Adults frequently attempted ≥4 AEDs, and the majority were using multiple AEDs when VGB was initiated. Due to disease-associated neurological disabilities, pre-existing blindness, and severe underlying medical problems, 40% of patients could not undergo baseline vision testing prior to VGB initiation in the registry, including 1,852 (41%) <17 years and 300 (35%) ≥17 years. Of the 352 (5%) patients with a baseline exam and at least 2 follow-up acuity tests, 18 demonstrated a reduction in visual acuity according to pre-defined criteria; of the 25 patients who could undergo consistent visual field testing, 4 met pre-defined criteria for visual field loss. Conclusions: The Sabril^® Registry has recorded the demographic and vision characteristics of US patients receiving VGB since 2009. Both adult and pediatric registry patients frequently attempted other epilepsy treatments prior to registry enrollment and are likely to receive other AEDs along with VGB. Reductions in visual acuity were detected in a small subset of registry patients with repeated, evaluable vision data. Some patients met the pre-defined criteria for visual field loss, though the numbers of patients that underwent consistent testing were too small to determine the frequency of VGB-associated field changes.