@article{28f3039ce9d1476daa20752234b9a3a9,
title = "High vigabatrin dosage is associated with lower risk of infantile spasms relapse among children with tuberous sclerosis complex",
abstract = "After initially successful treatment of infantile spasms, the long-term cumulative risk of relapse approaches 50%, and there is no established protocol to mitigate this risk. Although vigabatrin may be an effective means to prevent relapse, there is little guidance as to ideal duration and dosage. Using a cohort of children with infantile spasms and tuberous sclerosis complex (TSC), we evaluated the potential association of post-response VGB treatment and the rate of infantile spasms relapse. Patients with infantile spasms and clinical response to vigabatrin were identified among a multicenter prospective observational cohort of children with TSC. For each patient we recorded dates of infantile spasms onset, response to vigabatrin, relapse (if any), and quantified duration and dosage of vigabatrin after response. Time to relapse as a function of vigabatrin exposure was evaluated using survival analyses. We identified 50 children who responded to VGB. During a median follow-up of 16.6 months (IQR 10.3–22.9), 12 (24%) patients subsequently relapsed after a median of 7.8 months (IQR 3.1–9.6). Relapse occurred after VGB discontinuation in four patients, and during continued VGB treatment in the remaining eight cases. In survival analyses, risk of relapse was unaffected by the presence or absence of VGB treatment (HR 0.31, 95%CI 0.01–28.4, P = 0.61), but weighted-average dosage was associated with marked reduction in relapse risk: Each 50 mg/kg/d increment in dosage was associated with 61% reduction in risk (HR 0.39, 95%CI 0.17 – 0.90, P = 0.026). This study suggests that the risk of infantile spasms relapse in TSC may be reduced by high-dose vigabatrin treatment.",
keywords = "Epileptic spasms, Secondary prevention, West syndrome",
author = "{on behalf of the Tuberous Sclerosis Complex Autism Center of Excellence Network} and Hussain, {Shaun A.} and Ernst Schmid and Peters, {Jurriaan M.} and Monisha Goyal and Bebin, {E. Martina} and Hope Northrup and Mustafa Sahin and Krueger, {Darcy A.} and Wu, {Joyce Y.} and Deborah Pearson and Williams, {Marian E.} and Ellen Hanson and Nicole Bing and Bridget Kent and Sarah O'Kelley and Rajna Filip-Dhima and Kira Dies and Stephanie Bruns and Benoit Scherrer and Gary Cutter and Murray, {Donna S.} and Roberds, {Steven L.}",
note = "Funding Information: Dr. Wu serves on the professional advisory board for the Tuberous Sclerosis Alliance; has received honoraria from and serves on the scientific advisory board and the speakers{\textquoteright} bureau for Novartis Pharmaceuticals Inc. and Lundbeck; and has received research support from the Tuberous Sclerosis Alliance, Novartis Pharmaceuticals Inc. , Today and Tomorrow Children{\textquoteright}s Fund, Department of Defense/ Congressionally Directed Medical Research Program , and the NIH (P20NS080199, U01NS082320, R01NS082649, U54NS092090, and R01 NS092595). Funding Information: Dr. Peters received research support from the NIH ( NIH P20 NS080199 , R01 NS079788 , and U01 NS082320 ). Funding Information: This study was supported by the National Institute of Neurological Diseases and Stroke (U01-NS082320, P20-NS080199) and the Tuberous Sclerosis Alliance. Dr. Hussain was also supported by the Elsie and Isaac Fogelman Endowment, the Hughes Family Foundation, and the UCLA Children's Discovery and Innovation Institute. Dr. Wu was supported by the National Institute of Neurological Diseases and Stroke (R01-NS082649), the Department of Defense (W81XWH-11-1-0365) Congressionally Directed Medical Research Program, and the Today's and Tomorrow's Children Fund from UCLA Mattel Children's Hospital. Dr. Sahin was supported by the Developmental Synaptopathies Consortium (U54NS092090), which is part of the NCATS Rare Diseases Clinical Research Network (RDCRN). RDCRN is an initiative of the Office of Rare Diseases Research (ORDR), the National Center for Advancing Translational Sciences (NCATS), funded through collaboration with NCATS, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, and the National Institute of Child Health and Human Development (NICHD). This study also utilized clinical research facilities and resources supported by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health Grant (8UL1TR000077 and UL1RR033176). Funding Information: Dr. Sahin has received research funding from Roche , Novartis , Pfizer , and LAM Therapeutics , and has served on the Scientific Advisory Board of Sage Therapeutics and the PTEN Research Foundation. In addition, he serves on the Professional Advisory Board of the Tuberous Sclerosis Alliance. Funding Information: This study was supported by the National Institute of Neurological Diseases and Stroke ( U01-NS082320 , P20-NS080199 ) and the Tuberous Sclerosis Alliance. Dr. Hussain was also supported by the Elsie and Isaac Fogelman Endowment , the Hughes Family Foundation , and the UCLA Children{\textquoteright}s Discovery and Innovation Institute . Dr. Wu was supported by the National Institute of Neurological Diseases and Stroke ( R01-NS082649 ), the Department of Defense ( W81XWH-11-1-0365 ) Congressionally Directed Medical Research Program , and the Today{\textquoteright}s and Tomorrow{\textquoteright}s Children Fund from UCLA Mattel Children{\textquoteright}s Hospital . Dr. Sahin was supported by the Developmental Synaptopathies Consortium ( U54NS092090 ), which is part of the NCATS Rare Diseases Clinical Research Network (RDCRN). RDCRN is an initiative of the Office of Rare Diseases Research (ORDR), the National Center for Advancing Translational Sciences (NCATS), funded through collaboration with NCATS , the National Institute of Mental Health , the National Institute of Neurological Disorders and Stroke, and the National Institute of Child Health and Human Development (NICHD) . This study also utilized clinical research facilities and resources supported by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health Grant ( 8UL1TR000077 and UL1RR033176 ). Funding Information: Dr. Hussain has received research support from the Epilepsy Therapy Project , the Milken Family Foundation , the Hughes Family Foundation, the Elsie and Isaac Fogelman Endowment, Eisai , Lundbeck , INSYS , GW Pharmaceuticals , UCB , and the NIH ( R34MH089299 ), and has received honoraria for service on the scientific advisory boards of Questcor, Mallinckrodt, Insys, UCB, and Upsher-Smith Labs, for service as a consultant to Eisai, UCB, and Mallinckrodt, and for service on the speakers{\textquoteright} bureau of Mallinckrodt. ",
year = "2018",
month = dec,
doi = "10.1016/j.eplepsyres.2018.09.016",
language = "English (US)",
volume = "148",
pages = "1--7",
journal = "Epilepsy Research",
issn = "0920-1211",
publisher = "Elsevier",
}