Abstracts

The Vigabatrin Infantile Spasms Study Group previously demonstrated that vigabatrin produces seizure cessation in patients with infantile spasms, particularly those with spasms secondary to tuberous sclerosis (Neurology 2001;57:1416-1421). This [italic]a priori[/italic] analysis evaluates the efficacy of vigabatrin by etiology of infantile spasms., A multicenter, randomized, single-blind study of 14 days with a 3-year, open-label, flexible dosing follow-up in patients with new-onset infantile spasms. Patients [underline][lt][/underline]2 years of age and who were na[iuml]ve to treatment with either adrenocorticotropic hormone, prednisone, or valproate were randomized to receive either high-dose (100-148 mg/kg/day) or low-dose (18-36 mg/kg/day) vigabatrin for 14 days. Doses were administered orally (tablets) on a BID regimen. Subgroup analysis of efficacy data was conducted by etiology. Specifically, outcomes of patients by etiology who were spasm free for 7 consecutive days and remained spasm free for the duration of the study based on caregiver assessment were evaluated., Evaluable patients by etiology included 38 tuberous sclerosis (17.2%), 57 cryptogenic (25.8%), and 126 symptomatic-other (57.0%). Response increased dramatically for all etiologies after approximately 2 weeks of vigabatrin therapy and continued to increase with treatment. Of interest were response rates for spasm cessation for 7 consecutive days and remaining spasm free during of the study period (up to 3 years): 73.7% for tuberous sclerosis, 71.9% for cryptogenic, and 49.6% for symptomatic-other. The median time to spasm free status (and remaining spasm free during study period) by etiology was 3 weeks for tuberous sclerosis, 9 weeks for cryptogenic, and 14 weeks for symptomatic-other. Approximate percentage of subjects who became spasm free and remained spasm free by 12 weeks was 32%, 58% and 72%, respectively. The safety profile of vigabatrin by etiology disclosed no differences between groups., Vigabatrin was effective in rapidly producing freedom of spasms for symptomatic, cryptogenic and tuberous sclerosis-induced infantile spasms. The median onset of spasm freedom for all patients in the study ranged from 3 to 14 weeks, and occurred as early as 3 weeks for patients with tuberous sclerosis. While a significant separation of effect between the etiology categories was seen, with tuberous sclerosis responding slightly faster, all groups exhibited a high and sustained response rate to vigabatrin treatment.
Previous studies have suggested efficacy of vigabatrin in tuberous sclerosis-induced infantile spasms. This large study also suggests efficacy in cryptogenic and symptomatic-other infantile spasms. These data suggest that vigabatrin may be considered as a first-line treatment for all etiologies of infantile spasms., (Supported by Ovation Pharmaceuticals, Inc.)