Abstracts

Rationale: Vigabatrin (VGB) was approved in the United States in August 2009 as adjunctive therapy for adult patients (pts) with refractory complex partial seizures (rCPS) who had responded inadequately to several alternative treatments and as monotherapy for pts 1 month to 2 years of age with infantile spasms (IS). An important safety issue for VGB is the risk of vision loss, which needs further characterization. To manage this risk appropriately, the FDA and Lundbeck Inc. require a comprehensive Risk Evaluation and Mitigation Strategy (REMS), including an ongoing patient registry, which was designed to assess incidence, prevalence, time to onset, progression, and severity of vision loss. Methods: VGB prescribers and pts are enrolled in the SHARE program (Support, Help and Resources for Epilepsy). Participation in SHARE and the registry is mandatory for prescribers and pts. Data on prescriber specialty/location, patient demographics, and clinical characteristics are collected. Pts are assigned unique identifiers, and all data are associated with these identifiers. Regular vision assessments are required throughout VGB therapy. They occur at baseline (?4 weeks after VGB initiation), at least every 3 months during therapy, and 3-6 months after VGB discontinuation. Visual results are entered into the database. If formal perimetry is conducted, copies of visual field recordings are submitted to SHARE. Spontaneous adverse events (AEs) are not collected via the registry, but rather are treated as post-marketing reports and triaged and submitted to the FDA, as appropriate. Visual assessment data are considered outcome measures, and will be summarized in REMS assessments for the FDA, as required. Mandatory benefit/risk assessments are conducted by treating physicians early in therapy (within 2-4 weeks for IS and 3 months for rCPS). For each patient, if the benefit of VGB exceeds the risk, the prescriber submits the appropriate SHARE form, and the patient then continues in the maintenance phase. Outcomes of benefit/risk assessments are entered into the database, and data are collected as long as pts receive VGB. A steering committee finalized the registry protocol and is overseeing its conduct. The committee has 6 external experts in epileptology, neuro-ophthalmology, and epidemiology, and 3 Lundbeck staff. The committee periodically reviews registry visual function data and spontaneously reported visual function AEs and SAEs, and advises the sponsor on data analysis, and execution of the overall REMS. Analyses will be completed every 6 months during the first year of the registry (2009-10), and then annually for 6 years thereafter. Results: As of Dec. 2009, 830 pts were enrolled, of which, 538 had IS, 246 had rCPS, and 39 had other diagnoses (as determined by treating physicians). At enrollment, ~50% had previously received or were currently receiving VGB. Conclusions: The registry provides information on vision monitoring results, including risk factors, which may guide treatment decisions. Encouraging enrollment numbers will be enhanced by ongoing mandatory registry recruitment and will be reported.