Open AccessGenomic and clinical predictors of lacosamide response in refractory epilepsies
Author(s) -
Heavin Sinéad B.,
McCormack Mark,
Wolking Stefan,
Slattery Lisa,
Walley Nicole,
Avbersek Andreja,
Novy Jan,
Sinha Saurabh R.,
Radtke Rod,
Doherty Colin,
Auce Pauls,
Craig John,
Johnson Michael R.,
Koeleman Bobby P. C.,
Krause Roland,
Kunz Wolfram S.,
Marson Anthony G.,
O'Brien Terence J.,
Sander Josemir W.,
Sills Graeme J.,
Stefansson Hreinn,
Striano Pasquale,
Zara Federico,
Depondt Chantal,
Sisodiya Sanjay,
Goldstein David,
Lerche Holger,
Cavalleri Gianpiero L.,
Delanty Norman
Publication year - 2019
Publication title -
epilepsia open
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.247
H-Index - 16
ISSN - 2470-9239
DOI - 10.1002/epi4.12360
Subject(s) - lacosamide , refractory (planetary science) , medicine , epilepsy , neuroscience , psychology , biology , psychiatry , astrobiology
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.