Abstracts

Infantile spasm (IS) is a rare and refractory form of childhood epilepsy often associated with poor developmental outcome. IS has been most commonly treated in the past with ACTH or prednisone. While steroid therapy can be initially effective, it does not work for all and some patients relapse. Side effects can be significant. The results from prospective and retrospective studies suggest that vigabatrin (VGB) is well tolerated and an effective treatment for IS. We herein report the efficacy of 220 subjects 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-dose (18-36 mg/kg/day) or high-dose (100-148 mg/kg/day) VGB. Subjects who were free of spasms for 7 consecutive days beginning within the first 14 days of therapy according to caregiver response and had no indication of spasms or hypsarrhythmia during an 8-hour video EEG recording were considered treatment responders. Time to response was also assessed. All efficacy analyses were conducted on the modified intent-to-treat cohort. Eighteen percent (40/220) of subjects treated with VGB were treatment responders by both clinical and video EEG criteria. Twenty-six percent (58/220) of subjects were treatment responders if the window for obtaining an EEG was relaxed to be more consistent with clinical practice. Eighty-eight percent of the 58 subjects remained spasm-free for the remainder of the study. The response rate for the primary efficacy endpoint was significantly greater for subjects in the high-dose treatment group (26% [28/106]) compared with subjects in the low-dose treatment group (11% [12/114]) ([italic]P[/italic]=.0023). In addition, subjects with an IS etiology of tuberous sclerosis (TS) had a greater response rate compared to subjects with etiologies of either symptomatic-other or cryptogenic (TS, 58% [22/38]; symptomatic, 20% [25/125]; cryptogenic, 37% [21/57]). Time-to-response analyses shows a clear separation in the response rate beginning at week 2. In all treatment and etiology groups, maximum spasm-free status, when achieved, occurred by approximately week 4. Vigabatrin is effective in treating IS, especially in subjects with a spasm etiology of tuberous sclerosis. In addition, the response rate of subjects in the high-dose treatment group was greater than the subjects in the low-dose treatment group. (Supported by Ovation Pharmaceuticals.)