Response to Second Treatments for Infantile Epileptic Spasms Syndrome: Data Analysis with an Innovative Statistical Approach
Abstract number :
1.33
Submission category :
4. Clinical Epilepsy / 4C. Clinical Treatments
Year :
2024
Submission ID :
1359
Source :
www.aesnet.org
Presentation date :
12/7/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Kristen Barbour, MD – University of California, San Diego
Shaun Hussain, MD, MS – UCLA Mattel Children's Hospital, David Geffen School of Medicine
Kelly Knupp, MD, MSCS, FAES – University of Colorado, Children’s Hospital Colorado
Anup Patel, MD, FAAN, FAES – Nationwide Children's Hospital, The Ohio State University
Elissa Yozawitz, MD – Albert Einstein College of Medicine
Courtney Wusthoff, MD – Stanford University
Elaine Wirrell, MD – Mayo Clinic
Ignacio Valencia, MD – Drexel University College of Medicine
Nilika Singhal, MD – University of California, San Francisco
Douglas Nordli, MD – University of Chicago
John Mytinger, MD, FAES – Nationwide Children's Hospital, The Ohio State University
Wendy Mitchell, MD – Children's Hospital Los Angeles
Cynthia Keator, MD – CookChildren's Health care System
Tobias Loddenkemper, MD – Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, USA
Chellamani Harini, MD – Boston Children's Hospital, Harvard Medical School
William Gaillard, MD – Children's National Hospital
Ivan Fernandez, MD – Boston Children's Hospital
Jason Coryell, MD – Oregon Health and Sciences University/Doernbecher Children's Hospital
Catherine Chu, MD – Massachusetts General Hospital/Harvard Medical School
Anne Berg, PhD – Northwestern University
Renée Shellhaas, MD, MS – Washington University in St. Louis
Zachary Grinspan, MD, MS – Weill Cornell Medicine
Rationale: Infantile epileptic spasms syndrome (IESS) is a severe early-life epileptic encephalopathy. The best known way to improve long-term outcomes is early and effective treatment. However, at least one-third of infants continue to have epileptic spasms despite receiving a standard therapy as first treatment (Lux et al., 2004; Lancet). There are no randomized clinical trials and few observational studies evaluating responses to second treatments when the first treatment fails. Data are needed to guide clinicians when making these critical decisions in this vulnerable population. The current study builds upon the work of Knupp et al. (2016; Epilepsia) by utilizing a larger dataset to evaluate the comparative effectiveness of second treatments for epileptic spasms allowing us to analyze additional treatment groups.
Methods: Infants with IESS between ages 2-24 months were prospectively enrolled by 21 pediatric epilepsy centers in the United States from 2012 to 2018. We analyzed data from infants who initially received standard therapy (adrenocorticotropic hormone [ACTH], corticosteroids, or vigabatrin), had continued or recurring epileptic spasms, and received a second treatment. We excluded those with tuberous sclerosis complex. Treatment groups included hormonal therapy followed by vigabatrin (reference), hormonal-to-hormonal, hormonal-to-nonstandard, vigabatrin-to-hormonal, and vigabatrin-to-nonstandard. Hormonal therapy included ACTH and corticosteroids. Nonstandard treatments included antiseizure medications and dietary therapy. Treatment groups were tested for differences in three-month clinical remission outcomes using a multivariable generalized estimating equations model adjusting for baseline demographic, clinical, and neurologic baseline covariates with inverse propensity score weighting.
Results: There were 153 infants who received a second treatment (Figure 1). The highest response rates 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%) groups (Table 1). In the multivariable model, compared to the hormonal-to-vigabatrin reference group, fewer infants had remission in both the hormonal-to-nonstandard group (odds ratio=0.04, 95% confidence interval=0.01–0.33) and hormonal-to-hormonal group (odds ratio=0.19, 95% confidence interval=0.04 – 0.86).
Conclusions: Our findings continue to support a clinical strategy of switching mechanisms when selecting a second medication for epileptic spasms (i.e., use vigabatrin if hormonal therapy fails; hormonal therapy if vigabatrin fails). Our results also support the use of standard over nonstandard therapies.
Funding: N/A
Clinical Epilepsy