Abstract
IMPORTANCE: More than half of infants with new-onset epilepsy have electroencephalo-graphic and clinical features that do not conform to known electroclinical syndromes (ie, nonsyndromic epilepsy). Levetiracetam and phenobarbital are the most commonly prescribed medications for epilepsy in infants, but their comparative effectiveness is unknown. OBJECTIVE: To compare the effectiveness of levetiracetam vs phenobarbital for nonsyndromic infantile epilepsy. DESIGN, SETTING, AND PARTICIPANTS: The Early Life Epilepsy Study - a prospective, multicenter, observational cohort study conducted from March 1, 2012, to April 30, 2015, in 17 US medical centers - enrolled infants with nonsyndromic epilepsy and a first afebrile seizure between 1 month and 1 year of age. EXPOSURES: Use of levetiracetam or phenobarbital as initial monotherapy within 1 year of the first seizure. MAIN OUTCOMES AND MEASURES: The binary outcome was freedom from monotherapy failure at 6 months, defined as no second prescribed antiepileptic medication and freedom from seizures beginning within 3 months of initiation of treatment. Outcomes were adjusted for demographics, epilepsy characteristics, and neurologic history, as well as for observable selection bias using propensity score weighting and for within-center correlation using generalized estimating equations. RESULTS: Of the 155 infants in the study (81 girls and 74 boys; medianage, 4.7 months [interquartile range, 3.0-7.1 months]), those treated with levetiracetam (n = 117) were older at the time of the first seizure than those treated with phenobarbital (n = 38) (median age, 5.2 months [interquartile range, 3.5-8.2 months] vs 3.0 months [interquartile range, 2.0-4.4 months]; P <.001). There were no other significant bivariate differences. Infants treated with levetiracetam were free from monotherapy failure more often than those treated with phenobarbital (47 [40.2%] vs 6 [15.8%]; P =.01). The superiority of levetiracetam over phenobarbital persisted after adjusting for covariates, observable selection bias, and within-center correlation (odds ratio, 4.2; 95% CI, 1.1-16; number needed to treat, 3.5 [95% CI, 1.7-60]). CONCLUSIONS AND RELEVANCE: Levetiracetam may have superior effectiveness compared with phenobarbital for initial monotherapy of nonsyndromic epilepsy in infants. If 100 infants who received phenobarbital were instead treated with levetiracetam, 44 would be free from monotherapy failure instead of 16 by the estimates in this study. Randomized clinical trials are necessary to confirm these findings.
Original language | English (US) |
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Pages (from-to) | 352-360 |
Number of pages | 9 |
Journal | JAMA Pediatrics |
Volume | 172 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2018 |
Funding
ported receiving grants from the Pediatric Epilepsy Research Foundation, Centers for Disease Control and Prevention, BAND Foundation, Epilepsy Research Fund, and Patient-Centered Outcomes Research Institute and reported having a financial relationship with the Nanette Laitman Clinical Scholars Program. Dr Shellhaas reported receiving grants from the Pediatric Epilepsy Research Foundation and the Patient-Centered Outcomes Research Institute; receiving personal fees from UpToDate; and serving on the Board of the Child Neurology Society and on the Steering Committee of the Pediatric Epilepsy Research Consortium. Dr Sullivan reported receiving grants from Zogenix Inc, Marinus Pharmceuticals, and Citizens United for Research in Epilepsy. Dr Wirrell reported having a financial consulting relationship with Sun Pharma. Dr Knupp reported receiving grants from the Pediatric Epilepsy Research Fund. Dr Wusthoff reported having a financial consulting relationship with Ceribell. Dr Loddenkemper reported serving on the Laboratory Accreditation Board for Long Term (Epilepsy and Intensive Care Unit) Monitoring, the Council (and as vice president) of the American Clinical Neurophysiology Society, and the American Board of Clinical Neurophysiology; serving as an associate editor for Seizure and as an associate editor for Wyllie’s Treatment of Epilepsy, 6th edition; being part of pending patent applications to detect and predict seizures and to diagnose epilepsy; receiving research support from the Epilepsy Research Fund, the American Epilepsy Society, the Epilepsy Foundation of America, the Epilepsy Therapy Project, the Patient-Centered Outcomes Research Institute, the Pediatric Epilepsy Research Foundation, Citizens United for Research in Epilepsy, and the HHV-6 Foundation; receiving research grants from Lundbeck, Eisai, Upsher-Smith, Acorda, Mallinckrodt, and Pfizer; and serving as a consultant for Zogenix, Engage, Sunovion, Upsher-Smith, and Lundbeck. Dr Millichap reported receiving personal fees from the American Academy of Neurology, UptoDate, BMJ Best Practice, and Invitae, Inc; receiving grants and personal fees from UCB Pharma; receiving personal fees and nonfinancial support from Mallinckrodt; and receiving personal fees from Esai. Dr Berg reported receiving a grant from the Pediatric Epilepsy Research Foundation. No other disclosures were reported. Funding/Support: This study was funded by the Pediatric Epilepsy Research Foundation.
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health