Heavin, SB;
McCormack, M;
Wolking, S;
Slattery, L;
Walley, N;
Avbersek, A;
Novy, J;
... Delanty, N; + view all
(2019)
Genomic and clinical predictors of lacosamide response in refractory epilepsies.
Epilepsia Open
10.1002/epi4.12360.
(In press).
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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.
| Type: | Article |
|---|---|
| Title: | Genomic and clinical predictors of lacosamide response in refractory epilepsies |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/epi4.12360 |
| Publisher version: | https://doi.org/10.1002/epi4.12360 |
| Language: | English |
| Additional information: | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/ |
| Keywords: | GWAS, lacosamide, pharmacogenomics, pharmacoresistance, refractory |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10085730 |
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