Fifteen years of real‐world data on the use of vigabatrin in individuals with infantile epileptic spasms syndrome

Abstract

ObjectiveTo evaluate our treatment algorithm for Infantile epileptic spasms syndrome used between 2000 and 2018. We initiated Vigabatrin (VGB), and steroids were added if the electroclinical response (spasms and EEG) to VGB was not obtained or incomplete.MethodsIndividuals with IESS treated with VGB were recruited from our hospital clinical data warehouse based on electronic health records (EHR) generated since 2009 and containing relevant keywords. We confirmed the diagnosis of IESS and clinical, EEG, imaging, and biological data were extracted from The EHR. We analyzed factors associated with short‐term response, time to response, relapse, time to relapse of spasms and the presence of spasms at last follow‐up.ResultsWe collected data from 198 individuals (female: 46.5%, spasm onset: 6[4.5‐10.3] months, follow‐up: 4.6[2.5‐7.6] years, median [Q1‐Q3]) including 129 (65.2%) with identifiable etiology. VGB was started 17[5‐57.5] days after spasm diagnosis. A total of 113 individuals were responders (57.1% of the cohort), 64 with VGB alone and 38 with VGB further combined to steroids (56.6% and 33.6% of responders, respectively). Among responders, 33(29%) experienced spasms’ relapses, mostly those with later onset of spasms (p=0.002) and those who received VGB for less than 24 months after spasms cessation compared to a longer duration of VGB (45% versus 12.8%, p=0.003). At follow‐up, 92 individuals were seizure free (46.5% of the whole cohort) including 26 free of therapy (13.1%). One hundred twelve individuals (56.6%) were still receiving VGB with a duration of 3.2[1.75‐5.7] years.SignificanceOur sequential protocol introducing VGB then adding steroids is an effective alternative to combined VGB‐steroids approach in IESS. It avoids steroid related adverse events, as well as those from VGB‐steroid combination. According to our data, a period of 7 days seems sufficient to assess VGB response and enables the addition of steroids rapidly if needed. Continuing VGB for 2 years may balance the risk of relapse and treatment‐induced adverse events.

Genetic Advancements in Infantile Epileptic Spasms Syndrome and Opportunities for Precision Medicine

“…Current first-line treatments of IESS include ACTH, prednisolone, and vigabatrin [ 6 ]. Based on prospective studies to date, the response rates for these treatments are as follows: 36.7 to 87% for ACTH, 11 to 70% for prednisolone, and 11 to 58% for vigabatrin [ 6 , 111 , 112 , 113 , 114 , 115 , 116 ]. The first two therapies focus on broadly targeting the immune-mediated pathogenesis of IESS, while vigabatrin targets the GABAergic network involved in the development of spasms.…”