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Efficacy and safety of eslicarbazepine acetate monotherapy in patients converting from carbamazepine
Author(s) -
Pazdera Ladislav,
Sperling Michael R.,
Harvey Jay H.,
Sam Maria C.,
Strom Laura A.,
Blum David,
Grinnell Todd,
Cheng Hailong
Publication year - 2018
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.14014
Subject(s) - tolerability , carbamazepine , medicine , adverse effect , nausea , somnolence , epilepsy , clinical endpoint , onset of action , anesthesia , discontinuation , randomized controlled trial , psychiatry
Summary Objective To evaluate the influence of prior use of carbamazepine ( CBZ ) and other antiepileptic drugs ( AED s) with a putatively similar mechanism of action (inhibition of voltage‐gated sodium channels; VGSC s) 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 [ VGSC i]) during baseline versus those who received other AED s. 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 VGSC i) during baseline, versus other AED s, was not statistically significant (hazard ratios were 1.49 for + CBZ vs − CBZ [ P = .10] and 1.27 for + VGSC i vs. − VGSC i [ P = .33]). Reductions in seizure frequency and responder rates were lower in patients who converted from CBZ or other VGSC i compared with those who converted from other AED s. 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.