Abstracts

Infantile spasm (IS) is a rare and refractory form of childhood epilepsy often associated with poor developmental outcome. IS was most commonly treated with ACTH or prednisone. While steroid therapy can be effective, it does not work for all and patients may relapse. Side effects can be significant. The results from prospective and retrospective studies suggest that vigabatrin (VGB) is well tolerated and effective for IS. We herein report side effects and safety profiles in 222 patients treated with VGB. This was a multicenter, randomized, single-blind study of up to 21 days duration with up to a 3-year open-label, dose-ranging follow-up. Subjects were less than 2 years of age with IS duration of 3 months or less and were not previously treated with ACTH, prednisone, or valproic acid. Subjects were randomized to either low- (18-36 mg/kg/day) or high-dose (100-148 mg/kg/day) VGB. AEs were coded using MedDRA for the safety cohort (n=222). The incidence of AEs and serious adverse events (SAEs) were classified by system/organ class, relation to VGB and severity of AE. AEs and SAEs were classified by dose group and IS etiology. Additional analyses included assessments of abnormal laboratory values and ophthalmologic examination results. Visual field testing was not performed due to patient age. The safety profile was similar in low- and high-dose treatment groups. Ninety-three percent (207/222) of subjects had at least 1 AE. Eighteen subjects discontinued VGB as a result of an AE. A total of 2002 AEs were reported; 12% were classified as VGB-related, 86% were classified as not VGB-related, and 2% were classified as unknown. Of the AE[apos]s classified as related to VGB, 67% were classified as mild, 30% moderate, 2% severe and 1% unknown. A total of 174 SAEs were reported with 34% of subjects having at least 1 SAE. The majority of SAEs (95%) were not considered to be VGB-related. Of the 5 SAEs considered to be VGB-related, 1 was GI disorders, 2 were infections and 2 were nervous system disorders. Most of the SAEs were considered to be serious due to hospitalization. One of 3 deaths that occurred was unexplained presumably due to epilepsy and conservatively categorized as VGB related. Sixty eye-related AEs were reported. Ten could have been retinal disturbances; 6 were classified as not reasonably related, 4 as possibly and none as related. VGB was well tolerated. Only 18 of 222 subjects discontinued VGB as a result of an AE; 6 were classified as unrelated to VGB. Most AEs were classified as mild and not related to VGB therapy. Most SAEs were considered serious because subjects with major pre-existing conditions needed to be hospitalized and only 2.9% of SAEs were classified as VGB-related. (Supported by Ovation Pharmaceuticals.)