Comparative effectiveness of second-line treatments for epileptic spasms

Objective: This study was undertaken to evaluate the response to second treatments for infantile epileptic spasms syndrome (IESS). Methods: Infants aged 2–24 months with IESS were prospectively enrolled in the National Infantile Spasms Cohort study at 21 pediatric epilepsy centers in the United States from 2012 to 2018. We analyzed data from infants who initially received standard treatment (hormonal therapy [adrenocorticotropic hormone, high-dose prednisolone] or vigabatrin), had continued or recurring epileptic spasms, and received a second treatment. We excluded those with tuberous sclerosis. Treatment groups included hormonal therapy followed by vigabatrin (reference), hormonal-to-hormonal, hormonal-to-nonstandard, vigabatrin-to-hormonal, and vigabatrin-to-nonstandard. Nonstandard treatments included other antiseizure medications and dietary therapy. Treatment groups were tested for differences in 3-month clinical remission using a binary logistic regression to estimate odds ratios (ORs). Results: There were 153 infants with IESS who received second treatments. The highest rates of 3-month remission were among infants in the hormonal-to-vigabatrin (22/65, 34%) and vigabatrin-to-hormonal (9/26, 35%) groups, followed by vigabatrin-to-nonstandard (3/10, 30%), hormonal-to-hormonal (4/22, 18%), and hormonal-to-nonstandard (1/30, 3.3%). Compared to the hormonal-to-vigabatrin group (reference), fewer infants had remission in the hormonal-to-nonstandard group (OR =.07, 95% confidence interval [CI] =.01–.53), and there was a trend toward fewer infants in the hormonal-to-hormonal group (OR =.43, 95% CI =.13–1.4, p =.17). Following initial hormonal treatment, the number needed to treat was three infants for one additional infant to have remission when treated with vigabatrin compared to nonstandard therapy as the second treatment. Significance: This updated analysis with an expanded sample size provided power for additional subgroup analysis. Overall response rates were low, and at best only one third had remission after second treatment. Results support a clinical strategy of switching mechanism of action when selecting a second medication for epileptic spasms (i.e., use vigabatrin after hormonal therapy, or hormonal therapy after vigabatrin). Our findings also support the use of standard over nonstandard therapies.