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

DOI
https://doi.org/10.1002/epi4.12360
Journal volume & issue
Vol. 4, no. 4
pp. 563 – 571

Abstract

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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.

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