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Genomic and clinical predictors of lacosamide response in refractory epilepsies

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 c...

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Autores principales: 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, Kunz, Wolfram S., Marson, Anthony G., O'Brien, Terence J., Sander, Josemir W., Sills, Graeme J., Stefansson, Hreinn, Striano, Pasquale, Zara, Federico, Depondt, Chantal, Sisodiya, Sanjay, Goldstein, David, Lerche, Holger, Cavalleri, Gianpiero L., Delanty, Norman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885661/
https://www.ncbi.nlm.nih.gov/pubmed/31819912
http://dx.doi.org/10.1002/epi4.12360
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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
Kunz, Wolfram S.
Marson, Anthony G.
O'Brien, Terence J.
Sander, Josemir W.
Sills, Graeme J.
Stefansson, Hreinn
Striano, Pasquale
Zara, Federico
Depondt, Chantal
Sisodiya, Sanjay
Goldstein, David
Lerche, Holger
Cavalleri, Gianpiero L.
Delanty, Norman
author_facet 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
Kunz, Wolfram S.
Marson, Anthony G.
O'Brien, Terence J.
Sander, Josemir W.
Sills, Graeme J.
Stefansson, Hreinn
Striano, Pasquale
Zara, Federico
Depondt, Chantal
Sisodiya, Sanjay
Goldstein, David
Lerche, Holger
Cavalleri, Gianpiero L.
Delanty, Norman
author_sort Heavin, Sinéad B.
collection PubMed
description 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.
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spelling pubmed-68856612019-12-09 Genomic and clinical predictors of lacosamide response in refractory epilepsies 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 Kunz, Wolfram S. Marson, Anthony G. O'Brien, Terence J. Sander, Josemir W. Sills, Graeme J. Stefansson, Hreinn Striano, Pasquale Zara, Federico Depondt, Chantal Sisodiya, Sanjay Goldstein, David Lerche, Holger Cavalleri, Gianpiero L. Delanty, Norman Epilepsia Open Full‐length Original Research 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. John Wiley and Sons Inc. 2019-09-25 /pmc/articles/PMC6885661/ /pubmed/31819912 http://dx.doi.org/10.1002/epi4.12360 Text en © 2019 The Authors. Epilepsia Open published by Wiley Periodicals Inc. on behalf of International League Against Epilepsy This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full‐length Original Research
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
Kunz, Wolfram S.
Marson, Anthony G.
O'Brien, Terence J.
Sander, Josemir W.
Sills, Graeme J.
Stefansson, Hreinn
Striano, Pasquale
Zara, Federico
Depondt, Chantal
Sisodiya, Sanjay
Goldstein, David
Lerche, Holger
Cavalleri, Gianpiero L.
Delanty, Norman
Genomic and clinical predictors of lacosamide response in refractory epilepsies
title Genomic and clinical predictors of lacosamide response in refractory epilepsies
title_full Genomic and clinical predictors of lacosamide response in refractory epilepsies
title_fullStr Genomic and clinical predictors of lacosamide response in refractory epilepsies
title_full_unstemmed Genomic and clinical predictors of lacosamide response in refractory epilepsies
title_short Genomic and clinical predictors of lacosamide response in refractory epilepsies
title_sort genomic and clinical predictors of lacosamide response in refractory epilepsies
topic Full‐length Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885661/
https://www.ncbi.nlm.nih.gov/pubmed/31819912
http://dx.doi.org/10.1002/epi4.12360
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