Epilepsia Open (Dec 2019)
Genomic and clinical predictors of lacosamide response in refractory epilepsies
- Sinéad 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 L. Cavalleri,
- Norman Delanty
Affiliations
- Sinéad B. Heavin
- School of Pharmacy and Biomolecular Sciences Royal College of Surgeons Dublin Ireland
- Mark McCormack
- School of Pharmacy and Biomolecular Sciences Royal College of Surgeons Dublin Ireland
- Stefan Wolking
- Department of Neurology and Epileptology Hertie Institute for Clinical Brain Research University of Tübingen Tübingen Germany
- Lisa Slattery
- School of Pharmacy and Biomolecular Sciences Royal College of Surgeons Dublin Ireland
- Nicole Walley
- Centre for Human Genome Variation Duke University Durham NC USA
- Andreja Avbersek
- Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology London UK
- Jan Novy
- Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology London UK
- Saurabh R. Sinha
- Centre for Human Genome Variation Duke University Durham NC USA
- Rod Radtke
- Centre for Human Genome Variation Duke University Durham NC USA
- Colin Doherty
- School of Medicine Trinity College Dublin Dublin Ireland
- Pauls Auce
- Department of Molecular and Clinical Pharmacology Institute of Translational Medicine University of Liverpool Liverpool UK
- John Craig
- Department of Neurosciences Belfast Health and Social Care Trust Belfast UK
- Michael R. Johnson
- Division of Brain Sciences Imperial College Faculty of Medicine London UK
- Bobby P. C. Koeleman
- Center of Molecular Medicine University Medical Center Utrecht Utrecht The Netherlands
- Roland Krause
- Luxembourg Centre for Systems Biomedicine University of Luxembourg Esch‐sur‐Alzette Luxembourg
- Wolfram S. Kunz
- Institute of Experimental Epileptology and Cognition Research and Department of Epileptology University of Bonn Bonn Germany
- Anthony G. Marson
- Department of Molecular and Clinical Pharmacology Institute of Translational Medicine University of Liverpool Liverpool UK
- Terence J. O'Brien
- The Departments of Neuroscience and Neurology The Alfred Hospital Monash University Victoria Australia
- Josemir W. Sander
- Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology London UK
- Graeme J. Sills
- Department of Molecular and Clinical Pharmacology Institute of Translational Medicine University of Liverpool Liverpool UK
- Hreinn Stefansson
- deCODE Genetics/Amgen Inc Reykjavik Iceland
- Pasquale Striano
- Pediatric Neurology and Muscular Diseases Unit DINOGMI‐Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health Institute "G. Gaslini" University of Genova Genova Italy
- Federico Zara
- Laboratory of Neurogenetics and Neuroscience Institute G. Gaslini Genova Italy
- EPIGEN Consortium
- EpiPGX Consortium
- Chantal Depondt
- Department of Neurology Hôpital Erasme Université Libre de Bruxelles Brussels Belgium
- Sanjay Sisodiya
- Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology London UK
- David Goldstein
- Institute for Genomic Medicine Columbia University New York NY USA
- Holger Lerche
- Department of Neurology and Epileptology Hertie Institute for Clinical Brain Research University of Tübingen Tübingen Germany
- Gianpiero L. Cavalleri
- School of Pharmacy and Biomolecular Sciences Royal College of Surgeons Dublin Ireland
- Norman Delanty
- School of Pharmacy and Biomolecular Sciences Royal College of Surgeons Dublin Ireland
- DOI
- https://doi.org/10.1002/epi4.12360
- Journal volume & issue
-
Vol. 4,
no. 4
pp. 563 – 571
Abstract
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.
Keywords
