Abstracts

Rationale: Vigabatrin (VGB) has been available in investigations since the mid 1980 s and was FDA approved in 2009 for the treatment of infantile spasms (IS) and refractory complex partial seizures (rCPS) in adults. Development and approval were prolonged due to concern for visual field restriction which may be irreversible. Efforts to mitigate this risk have resulted in the use of lower doses, close monitoring of visual fields, and limited exposure time. Our patients with rCPS have received VGB over 6.5 years in a study protocol (VGPR0098) in 1994-2000 (S1), in a prospective vision protocol (13098A) (S2), and in compassionate or clinical use (CU). We wished to evaluate our experience with VGB over this time period. This study reports the adult experience.Methods: Using our EMR system, we queried charts for past or present VGB use and prior study charts. Data abstracted included reason for use, age, seizure type, dose, response to therapy, status of therapeutic use at this time, adverse events (AE), and efficacy.Results: Thirty-three adults who are currently receiving, or in the past have received VGB in polytherapy, were identified. Reason for use was IS in 4 and rCPS in 29. Age range at this time is 18-66, median 36, for 13 men and 20 women. Diagnosis was LGS in 2 and TS in 4. Seventeen patients were in S1, an efficacy trial, and 3 are in S2. Four patients received VGB for IS as infants. Others received VGB in CU or SHARE program. Doses overall ranged between 1000-6000 mg/day, median 3000 mg/day; 12 patients in S1 received > 3000 mg/ day. Reported AEs were 1 asymptomatic peripheral vision restriction in compassionate use 10 years ago, 1 behavior change, and 2 rashes. No patients in the prospective S2 study have had documented vision loss to date. No significant efficacy was noted in 12, while 20 patients (67%) improved in seizure frequency and/or severity. Seizure freedom was noted by 2 patients (6%) prior to the end of S1. Patients who experienced efficacy ranged in age 19-63, median 41. Of those who experienced efficacy, 61% were at doses 3000 mg. Patients who did not respond tended to have multi-focal EEG onset. Eight patients had subsequent resective surgery, 7 of whom had reported efficacy. Four had corpus callosotomy, and 8 had VNS. Reasons for discontinuation, if known, were end of S1 study (6), lack of efficacy (7), adverse event (2), loss of prior efficacy (3), increased seizures (2), and patient choice (2). Eight patients have been lost to follow-up. There were no clear predictors of response.Conclusions: VGB offers an effective medical treatment option for adults with refractory complex partial seizures. Physicians should follow recommended guidelines for use until the mechanism and significance of visual field restriction is clearly defined. VGB therapy has been well tolerated and provided improved control in a large percentage of refractory patients.