Oxcarbazepine Use and the Risk of Infantile Spasms Among Children with Epilepsy
Abstract number :
3.288
Submission category :
7. Anti-seizure Medications / 7C. Cohort Studies
Year :
2021
Submission ID :
1825751
Source :
www.aesnet.org
Presentation date :
12/6/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:50 AM
Authors :
Zachary Grinspan, MD - Weill Cornell Medicine; Jea Young Min, PharmD, MPH, PhD – Weill Cornell Medical College; Erika Axeen, MD – University of Virginia; Natasha Basma – Weill Cornell Medical College; Anne Berg, PhD – Ann & Robert H. Lurie Children's Hospital of Chicago; Sonam Bhalla, MD – Emory University; Jeffrey Bolton, MD – Boston Children's Hospital; Jason Coryell, MD – Oregon Health & Science University; Scott Demarest, MD – Children's Hospital Colorado; William Gaillard, MD – Children's National; Howard Goodkin, MD, PhD – University of Virginia; Shaun Hussain – University of California Los Angeles; Tobias Loddenkemper, MD – Boston Children's Hospital; Juma Mbwana, MD – Children's National; Lindsey Morgan, MD – Seattle Children's; Anup Patel, MD – Nationwide Children's Hospital; Scott Perry, MD – Cook Children's; Tristan Sands, MD, PhD – Columbia University; Renee Shellhaas, MD, MS – Michigan Medicine; Nilika Singhal, MD – University of California San Francisco; Dmitry Tchapyjnikov, MD – Duke University; Alan Wu – Weill Cornell Medical College; Elissa Yozawitz, MD – Montefiore Medical Center; Muhammad Zafar – Duke University
Rationale: A recent study by Hussain and colleagues suggested that the use of sodium channel blockers, such as oxcarbazepine, in infants may increase the risk for infantile spasms syndrome (ISS). We sought to investigate a clinical scenario in which infants with epilepsy might be prescribed levetiracetam or oxcarbazepine with equipoise. To do so, we retrospectively compared the risk of ISS in young infants who received phenobarbital, a common first-line agent for seizures, and who then received either oxcarbazepine or levetiracetam as a second anti-seizure medication (ASM). Oxcarbazepine was selected because it is the most commonly used sodium channel blocker in infants.
Methods: We conducted a retrospective cohort study using the Pediatric Epilepsy Learning Health System (PELHS) data including electronic health record data for children with epilepsy from 13 US sites. We identified children with a new electronic prescription or inpatient administration for phenobarbital between 0 and 2 months of age, and those who had a subsequent prescription or inpatient administration (second ASM) for oxcarbazepine or levetiracetam by 8 months of age. All patients were followed until the first date of ISS diagnosis, last healthcare encounter date, death, or 18 months of age, whichever came first. The risk of ISS was compared in patients who started oxcarbazepine versus levetiracetam in a propensity score (PS) weighted Cox proportional hazards model. The PS model adjusted for multiple baseline covariates including age at first phenobarbital prescription, age at first oxcarbazepine or levetiracetam prescription, race, ethnicity, sex, Pediatric Medical Complexity Algorithm2 score, and etiological co-diagnoses including hypoxic-ischemic encephalopathy (HIE), stroke, and other brain lesions (based on ICD-10 codes). Multiple imputation accounted for missing covariates.
Results: There were 507 children in the PELHS data who received phenobarbital as their first ASM in the first 60 days of life. Of those children, 411 subsequently received either oxcarbazepine (n=31) or levetiracetam (n=380) before 8 months of age and were included in the study (Table). Demographics are summarized in the table. The median age at first phenobarbital exposure was 7 days (interquartile range [IQR] 2-27), and the median age at subsequent oxcarbazepine or levetiracetam exposure was 28 days (IQR 7-68). Etiological co-diagnoses included HIE (21%), stroke (15%), and other brain lesions (25%). During follow-up, there were 4 (12.9%) cases of ISS in the oxcarbazepine group versus 37 (9.7%) cases in the levetiracetam group. The risk of ISS was higher for oxcarbazepine compared to levetiracetam after accounting for potential confounders (adjusted hazard ratio 2.84, 95% CI 1.40-5.78) (Figure).
Conclusions: In this preliminary analysis, oxcarbazepine was associated with a greater risk of ISS compared to levetiracetam. Though the sample size was small and residual confounding cannot be ruled out, our study results warrant further investigation on whether sodium channel blockers may be causally linked to ISS in infants.
Funding: Please list any funding that was received in support of this abstract.: Pediatric Epilepsy Research Foundation.
Anti-seizure Medications