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Genomic and clinical predictors of lacosamide response in refractory epilepsies

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posted on 16.04.2021, 10:47 by Sinead B Heavin, Mark McCormack, Stefan Wolking, Lisa Slattery, Nicole Walley, Andreja Avbersek, Jan Novy, Saurabh R Sinha, Rod Radtke, Colin Doherty, Pauls Auce, John Craig, Michael R Johnson, Bobby P C Koeleman, Roland Krause, Wolfram S Kunz, Anthony G Marson, Terence J O'Brien, Josemir W Sander, Graeme J Sills, Hreinn Stefansson, Pasquale Striano, Federico Zara, EPIGEN Consortium, EpiPGX Consortium, Chantal Depondt, Sanjay Sisodiya, David Goldstein, Holger Lerche, Gianpiero Cavalleri, Norman Delanty

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.

Funding

Marie‐Curie Individual Fellowship, European Commission, Grant/Award Number: 751761

Science Foundation Ireland, Grant/Award Number: 13/ CDA/2223 and 16/RC/3948

"EpiPGX"; UK Department of Health's Biomedical Research Centres'

Dr Marvin Weil Epilepsy Research Fund

FP7 Health, Grant/Award Number: 279062

Clinician Scientist Program of the Medical Faculty of the University of Tübingen, Grant/ Award Number: 418‐0‐0

History

Comments

The original article is available at https://onlinelibrary.wiley.com

Published Citation

Heavin SB, McCormack M, Wolking S, Slattery L, Walley N, Avbersek A, Novy J, Sinha SR, Radtke R, Doherty C, Auce P, Craig J, Johnson MR, Koeleman BPC, Krause R, Kunz WS, Marson AG, O'Brien TJ, Sander JW, Sills GJ, Stefansson H, Striano P, Zara F; EPIGEN Consortium; EpiPGX Consortium, Depondt C, Sisodiya S, Goldstein D, Lerche H, Cavalleri GL, Delanty N. Genomic and clinical predictors of lacosamide response in refractory epilepsies. Epilepsia Open. 2019;4(4):563-571.

Publication Date

11 September 2019

PubMed ID

31819912

Department/Unit

  • Beaumont Hospital
  • FutureNeuro Centre
  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Neurological and Psychiatric Disorders

Publisher

Wiley

Version

  • Published Version (Version of Record)

Licence

Exports