4.2 Article

Genomic and clinical predictors of lacosamide response in refractory epilepsies

期刊

EPILEPSIA OPEN
卷 4, 期 4, 页码 563-571

出版社

WILEY
DOI: 10.1002/epi4.12360

关键词

GWAS; lacosamide; pharmacogenomics; pharmacoresistance; refractory

资金

  1. Marie-Curie Individual Fellowship, European Commission [751761]
  2. Science Foundation Ireland [13/CDA/2223, 16/RC/3948]
  3. FP7 Health [279062]
  4. UK Department of Health's Biomedical Research Centres'
  5. Dr Marvin Weil Epilepsy Research Fund
  6. Clinician Scientist Program of the Medical Faculty of the University of Tubingen [418-0-0]
  7. MRC [G0800637] Funding Source: UKRI
  8. Science Foundation Ireland (SFI) [13/CDA/2223] Funding Source: Science Foundation Ireland (SFI)
  9. Marie Curie Actions (MSCA) [751761] Funding Source: Marie Curie Actions (MSCA)

向作者/读者索取更多资源

ObjectiveClinical and genetic predictors of response to antiepileptic drugs (AEDs) are largely unknown. We examined predictors of lacosamide response in a real-world clinical setting. MethodsWe 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. ResultsMost 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. SignificanceNo genetic predictor of lacosamide response was identified. Patients with refractory GGE might benefit from treatment with lacosamide.

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