@article{efd06829c8ce4b2292554899718d9706,
title = "Genomic and clinical predictors of lacosamide response in refractory epilepsies",
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.",
keywords = "GWAS, lacosamide, pharmacogenomics, pharmacoresistance, refractory",
author = "Heavin, {Sin{\'e}ad B.} and Mark McCormack and Stefan Wolking and Lisa Slattery and Nicole Walley and Andreja Avbersek and Jan Novy and Sinha, {Saurabh R.} and Rod Radtke and Colin Doherty and Pauls Auce and John Craig and Johnson, {Michael R.} and Koeleman, {Bobby P.C.} and Roland Krause and Kunz, {Wolfram S.} and Marson, {Anthony G.} and O'Brien, {Terence J.} and Sander, {Josemir W.} and Sills, {Graeme J.} and Hreinn Stefansson and Pasquale Striano and Federico Zara and Chantal Depondt and Sanjay Sisodiya and David Goldstein and Holger Lerche and Cavalleri, {Gianpiero L.} and Norman Delanty",
note = "Funding Information: Parts of the computational analysis were performed on the high‐performance computer system of the University of Luxembourg ( https://hpc.uni.lu ). GLC was supported by Science Foundation Ireland, grants 13/CDA/2223 and 16/RC/3948. MMC was supported by a Marie‐Curie Individual Fellowship (No. 751761) from the European Commission. The EpiPGX Consortium was funded by FP7 Grant 279062 “EpiPGX” from the European Commission. SMS and JWS are based at the NIHR University College London Hospitals Comprehensive Biomedical Research Centre, which receives a proportion of funding from the UK Department of Health's Biomedical Research Centres' funding scheme. SMS and JWS receive support from the UK Epilepsy Society. JWS receives support from the Dr Marvin Weil Epilepsy Research Fund. SW was supported by the Clinician Scientist Program of the Medical Faculty of the University of T{\"u}bingen (418‐0‐0). We would also like to acknowledge the patients, carers, and clinical staff for making this research possible. Funding Information: Parts of the computational analysis were performed on the high-performance computer system of the University of Luxembourg (https://hpc.uni.lu). GLC was supported by Science Foundation Ireland, grants 13/CDA/2223 and 16/RC/3948. MMC was supported by a Marie-Curie Individual Fellowship (No. 751761) from the European Commission. The EpiPGX Consortium was funded by FP7 Grant 279062 ?EpiPGX? from the European Commission. SMS and JWS are based at the NIHR University College London Hospitals Comprehensive Biomedical Research Centre, which receives a proportion of funding from the UK Department of Health's Biomedical Research Centres' funding scheme. SMS and JWS receive support from the UK Epilepsy Society. JWS receives support from the Dr Marvin Weil Epilepsy Research Fund. SW was supported by the Clinician Scientist Program of the Medical Faculty of the University of T?bingen (418-0-0). We would also like to acknowledge the patients, carers, and clinical staff for making this research possible. Publisher Copyright: {\textcopyright} 2019 The Authors. Epilepsia Open published by Wiley Periodicals Inc. on behalf of International League Against Epilepsy",
year = "2019",
month = dec,
day = "1",
doi = "10.1002/epi4.12360",
language = "English",
volume = "4",
pages = "563--571",
number = "4",
}