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 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.
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
CommentsThe original article is available at https://onlinelibrary.wiley.com
Published CitationHeavin 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 Date11 September 2019
- Beaumont Hospital
- FutureNeuro Centre
- School of Pharmacy and Biomolecular Sciences
- Neurological and Psychiatric Disorders
- Published Version (Version of Record)