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Comparative effectiveness of second-line treatments for epileptic spasms
Kristen Barbour1, Shaun A Hussain2, Kelly G Knupp3
1University of California, San Diego, La Jolla, California, USA.
Insights
Second treatments for infantile epileptic spasms syndrome (IESS) show low remission rates. Switching medication types, such as hormonal therapy to vigabatrin or vice versa, offers the best chance for remission in infants with IESS.
Area of Science:
- Pediatric Neurology
- Epileptology
- Clinical Pharmacology
Background:
- Infantile epileptic spasms syndrome (IESS) is a severe epilepsy syndrome in infants.
- Treatment response to initial therapies can be variable, necessitating evaluation of second-line treatment strategies.
- Understanding the efficacy of different second treatment sequences is crucial for optimizing patient outcomes.
Purpose of the Study:
- To evaluate the effectiveness of various second treatment regimens for infantile epileptic spasms syndrome (IESS).
- To compare remission rates between different sequences of standard and nonstandard therapies in infants with IESS.
- To identify optimal second-line treatment strategies for IESS based on clinical response.
Main Methods:
- Prospective enrollment of 153 infants (aged 2-24 months) with IESS across 21 US pediatric epilepsy centers (2012-2018).
- Analysis of infants who received standard first-line treatment (hormonal therapy or vigabatrin) followed by a second treatment, excluding those with tuberous sclerosis.
- Comparison of 3-month clinical remission rates across treatment groups (hormonal-to-vigabatrin, hormonal-to-hormonal, hormonal-to-nonstandard, vigabatrin-to-hormonal, vigabatrin-to-nonstandard) using binary logistic regression.
Main Results:
- The highest 3-month remission rates were observed in the hormonal therapy to vigabatrin (34%) and vigabatrin to hormonal therapy (35%) groups.
- Hormonal therapy to nonstandard treatment showed significantly lower remission rates (3.3%) compared to the hormonal therapy to vigabatrin reference group (OR = .07).
- A trend towards lower remission was noted in the hormonal therapy to hormonal therapy group (18%) compared to hormonal therapy to vigabatrin (OR = .43).
Conclusions:
- Overall response rates to second treatments for IESS remain low, with a maximum of one-third of infants achieving remission.
- Switching the mechanism of action for the second treatment (e.g., hormonal therapy to vigabatrin or vice versa) is a supported clinical strategy.
- The study reinforces the preference for standard therapies over nonstandard options as second-line treatments for IESS.
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.
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