Article (Scientific journals)
Genomic and clinical predictors of lacosamide response in refractory epilepsies
Heavin, Sinéad B.; McCormack, Mark; Wolking, Stefan et al.
2019In Epilepsia Open, 0 (0)
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Abstract :
[en] Abstract Objective Clinical and genetic predictors of response to antiepileptic drugs (AEDs) are largely unknown. We examined predictors of lacosamide response in a real-world clinical setting. Methods We tested the association of clinical predictors with treatment response using regression modeling in a cohort of people with refractory epilepsy. Genetic assessment for lacosamide response was conducted via genome-wide association studies and exome studies, comprising 281 candidate genes. Results Most patients (479/483) were treated with LCM in addition to other AEDs. Our results corroborate previous findings that patients with refractory genetic generalized epilepsy (GGE) may respond to treatment with LCM. No clear clinical predictors were identified. We then compared 73 lacosamide responders, defined as those experiencing greater than 75% seizure reduction or seizure freedom, to 495 nonresponders (<25% seizure reduction). No variants reached the genome-wide significance threshold in our case-control analysis. Significance No genetic predictor of lacosamide response was identified. Patients with refractory GGE might benefit from treatment with lacosamide.
Disciplines :
Neurology
Author, co-author :
Heavin, Sinéad B.
McCormack, Mark
Wolking, Stefan
Slattery, Lisa
Walley, Nicole
Avbersek, Andreja
Novy, Jan
Sinha, Saurabh R.
Radtke, Rod
Doherty, Colin
Auce, Pauls
Craig, John
Johnson, Michael R.
Koeleman, Bobby P. C.
Krause, Roland  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Kunz, Wolfram S.
Marson, Anthony G.
O'Brien, Terence J.
Sander, Josemir W.
Sills, Graeme J.
Stefansson, Hreinn
Striano, Pasquale
Zara, Federico
EPIGEN Consortium
EpiPGX Consortium
Depondt, Chantal
Sisodiya, Sanjay
Goldstein, David
Lerche, Holger
Cavalleri, Gianpiero L.
Delanty, Norman
More authors (21 more) Less
External co-authors :
yes
Language :
English
Title :
Genomic and clinical predictors of lacosamide response in refractory epilepsies
Publication date :
2019
Journal title :
Epilepsia Open
ISSN :
2470-9239
Publisher :
Wiley, United States
Volume :
0
Issue :
0
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
European Projects :
FP7 - 279062 - EPIPGX - Epilepsy Pharmacogenomics: delivering biomarkers for clinical use
Funders :
CE - Commission Européenne [BE]
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since 25 September 2019

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