Efficacy and safety of eslicarbazepine acetate monotherapy in patients converting from carbamazepine

Ladislav Pazdera, Michael R. Sperling, Jay H. Harvey, Maria C. Sam, Laura A. Strom, David Blum, Todd Grinnell, Hailong Cheng

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: To evaluate the influence of prior use of carbamazepine (CBZ) and other antiepileptic drugs (AEDs) with a putatively similar mechanism of action (inhibition of voltage-gated sodium channels; VGSCs) on seizure outcomes and tolerability when converting to eslicarbazepine acetate (ESL), using data pooled from 2 controlled conversion-to-ESL monotherapy trials (studies: 093-045, 093-046). Methods: Adults with treatment-resistant focal (partial-onset) seizures were randomized 2:1 to ESL 1600 or 1200 mg once daily. The primary efficacy endpoint was study exit (meeting predefined exit criteria related to worsening seizure control) versus an historical control group. Other endpoints included change in seizure frequency, responder rate, and tolerability. Endpoints were analyzed for subgroups of patients who received CBZ (or any VGSC inhibitor [VGSCi]) during baseline versus those who received other AEDs. Results: Of 365 patients in the studies, 332 were evaluable for efficacy. The higher risk of study exit in the subgroups that received CBZ (or any VGSCi) during baseline, versus other AEDs, was not statistically significant (hazard ratios were 1.49 for +CBZ vs −CBZ [P =.10] and 1.27 for +VGSCi vs. −VGSCi [P =.33]). Reductions in seizure frequency and responder rates were lower in patients who converted from CBZ or other VGSCi compared with those who converted from other AEDs. There were no notable differences in overall tolerability between subgroups, but the incidence of some adverse events (eg, dizziness, somnolence, nausea) differed between subgroups and/or between treatment periods. Significance: Baseline use of CBZ or other major putative VGSC inhibitors did not appear to significantly increase the risk of study exit due to worsening seizure control, or to increase the frequency of side effects when converting to ESL monotherapy. However, bigger improvements in efficacy may be possible in patients converting to ESL monotherapy from an AED regimen that does not include a VGSC inhibitor.

Original languageEnglish (US)
Pages (from-to)704-714
Number of pages11
JournalEpilepsia
Volume59
Issue number3
DOIs
StatePublished - Mar 1 2018

Fingerprint

Carbamazepine
Seizures
Anticonvulsants
Safety
Voltage-Gated Sodium Channels
Dizziness
eslicarbazepine acetate
Nausea
Control Groups
Incidence
Therapeutics

Keywords

  • antiepileptic drugs
  • focal seizures
  • refractory epilepsy
  • switching

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Pazdera, L., Sperling, M. R., Harvey, J. H., Sam, M. C., Strom, L. A., Blum, D., ... Cheng, H. (2018). Efficacy and safety of eslicarbazepine acetate monotherapy in patients converting from carbamazepine. Epilepsia, 59(3), 704-714. https://doi.org/10.1111/epi.14014

Efficacy and safety of eslicarbazepine acetate monotherapy in patients converting from carbamazepine. / Pazdera, Ladislav; Sperling, Michael R.; Harvey, Jay H.; Sam, Maria C.; Strom, Laura A.; Blum, David; Grinnell, Todd; Cheng, Hailong.

In: Epilepsia, Vol. 59, No. 3, 01.03.2018, p. 704-714.

Research output: Contribution to journalArticle

Pazdera, L, Sperling, MR, Harvey, JH, Sam, MC, Strom, LA, Blum, D, Grinnell, T & Cheng, H 2018, 'Efficacy and safety of eslicarbazepine acetate monotherapy in patients converting from carbamazepine', Epilepsia, vol. 59, no. 3, pp. 704-714. https://doi.org/10.1111/epi.14014
Pazdera, Ladislav ; Sperling, Michael R. ; Harvey, Jay H. ; Sam, Maria C. ; Strom, Laura A. ; Blum, David ; Grinnell, Todd ; Cheng, Hailong. / Efficacy and safety of eslicarbazepine acetate monotherapy in patients converting from carbamazepine. In: Epilepsia. 2018 ; Vol. 59, No. 3. pp. 704-714.
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N2 - Objective: To evaluate the influence of prior use of carbamazepine (CBZ) and other antiepileptic drugs (AEDs) with a putatively similar mechanism of action (inhibition of voltage-gated sodium channels; VGSCs) on seizure outcomes and tolerability when converting to eslicarbazepine acetate (ESL), using data pooled from 2 controlled conversion-to-ESL monotherapy trials (studies: 093-045, 093-046). Methods: Adults with treatment-resistant focal (partial-onset) seizures were randomized 2:1 to ESL 1600 or 1200 mg once daily. The primary efficacy endpoint was study exit (meeting predefined exit criteria related to worsening seizure control) versus an historical control group. Other endpoints included change in seizure frequency, responder rate, and tolerability. Endpoints were analyzed for subgroups of patients who received CBZ (or any VGSC inhibitor [VGSCi]) during baseline versus those who received other AEDs. Results: Of 365 patients in the studies, 332 were evaluable for efficacy. The higher risk of study exit in the subgroups that received CBZ (or any VGSCi) during baseline, versus other AEDs, was not statistically significant (hazard ratios were 1.49 for +CBZ vs −CBZ [P =.10] and 1.27 for +VGSCi vs. −VGSCi [P =.33]). Reductions in seizure frequency and responder rates were lower in patients who converted from CBZ or other VGSCi compared with those who converted from other AEDs. There were no notable differences in overall tolerability between subgroups, but the incidence of some adverse events (eg, dizziness, somnolence, nausea) differed between subgroups and/or between treatment periods. Significance: Baseline use of CBZ or other major putative VGSC inhibitors did not appear to significantly increase the risk of study exit due to worsening seizure control, or to increase the frequency of side effects when converting to ESL monotherapy. However, bigger improvements in efficacy may be possible in patients converting to ESL monotherapy from an AED regimen that does not include a VGSC inhibitor.

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