Zachary M Grinspan1,2,3, Renée A Shellhaas4, Jason Coryell5,6, Joseph E Sullivan7, Elaine C Wirrell8, John R Mytinger9, William D Gaillard10, Eric H Kossoff11,12, Ignacio Valencia13, Kelly G Knupp14,15, Courtney Wusthoff16, Cynthia Keator17, Nicole Ryan18, Tobias Loddenkemper19, Catherine J Chu20, Edward J Novotny21,22,23,24, John Millichap25,26, Anne T Berg25,26. 1. Department of Healthcare Policy & Research, Weill Cornell Medicine, New York, New York. 2. Department of Pediatrics, Weill Cornell Medicine, New York, New York. 3. New York-Presbyterian Komansky Children's Hospital, New York, New York. 4. Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor. 5. Department of Pediatrics, Oregon Health & Sciences University, Portland. 6. Department of Neurology, Oregon Health & Sciences University, Portland. 7. Department of Neurology, University of California, San Francisco. 8. Department of Neurology, Mayo Clinic, Rochester, Minnesota. 9. Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus. 10. Department of Neurology, Children's National Health System, George Washington University School of Medicine, Washington, DC. 11. Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland. 12. Department of Pediatrics, Johns Hopkins Hospital, Baltimore, Maryland. 13. Section of Neurology, St. Christopher's Hospital for Children, Drexel University College of Medicine, Philadelphia, Pennsylvania. 14. Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora. 15. Department of Neurology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora. 16. Division of Child Neurology, Stanford University, Palo Alto, California. 17. Comprehensive Epilepsy Program, Jane and John Justin Neuroscience Center, Cook Children's Medical Center, Fort Worth, Texas. 18. Division of Neurology, The Children's Hospital of Philadelphia, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia. 19. Division of Epilepsy and Clinical Neurophysiology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts. 20. Department of Neurology, Massachusetts General Hospital, Boston. 21. Division of Pediatric Neurology, Seattle Children's Hospital, Seattle, Washington. 22. Department of Neurology, University of Washington, Seattle. 23. Department of Pediatrics, University of Washington, Seattle. 24. Center for Integrative Brain Research, University of Washington, Seattle. 25. Epilepsy Center, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois. 26. Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Abstract
Importance: More than half of infants with new-onset epilepsy have electroencephalographic 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; median age, 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.
Importance: More than half of infants with new-onset epilepsy have electroencephalographic 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; median age, 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.
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Authors: Zachary M Grinspan; Kelly G Knupp; Anup D Patel; Elissa G Yozawitz; Courtney J Wusthoff; Elaine Wirrell; Ignacio Valencia; Nilika S Singhal; Douglas R Nordli; John R Mytinger; Wendy Mitchell; Cynthia G Keator; Tobias Loddenkemper; Shaun A Hussain; Chellamani Harini; William D Gaillard; Ivan S Fernandez; Jason Coryell; Catherine J Chu; Anne T Berg; Renee A Shellhaas Journal: Neurology Date: 2021-07-15 Impact factor: 11.800