Genomic and clinical predictors of lacosamide response in refractory epilepsies

Heavin, S. B. et al. (2019) Genomic and clinical predictors of lacosamide response in refractory epilepsies. Epilepsia Open, 4(4), pp. 563-571. (doi: 10.1002/epi4.12360) (PMID:31819912) (PMCID:PMC6885661)

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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.

Item Type:Articles
Additional Information: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 Tübingen (418‐0‐0).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Auce, Dr Pauls and Sills, Dr Graeme
Authors: Heavin, S. B., McCormack, M., Wolking, S., Slattery, L., Walley, N., Avbersek, A., Novy, J., Sinha, S. R., Radtke, R., Doherty, C., Auce, P., Craig, J., Johnson, M. R., Koeleman, B. P.C., Krause, R., Kunz, W. S., Marson, A. G., O'Brien, T. J., Sander, J. W., Sills, G. J., Stefansson, H., Striano, P., Zara, F., EPIGEN Consortium, ., EpiPGX Consortium, ., Depondt, C., Sisodiya, S., Goldstein, D., Lerche, H., Cavalleri, G. L., and Delanty, N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Epilepsia Open
Publisher:Wiley
ISSN:2470-9239
ISSN (Online):2470-9239
Published Online:25 September 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Epilepsia Open 4(4):563-571
Publisher Policy:Reproduced under a Creative Commons License

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