Long-term efficacy and safety of eslicarbazepine acetate monotherapy for adults with newly diagnosed focal epilepsy: An open-label extension study

Epilepsia. 2020 Oct;61(10):2129-2141. doi: 10.1111/epi.16666. Epub 2020 Sep 17.

Abstract

Objective: To assess the efficacy, safety, and tolerability of eslicarbazepine acetate (ESL) monotherapy during long-term treatment.

Methods: An open-label extension (OLE) study was conducted in adults completing a phase 3, randomized, double-blind, noninferiority trial, during which they had received monotherapy with either once-daily ESL or twice-daily controlled-release carbamazepine (CBZ-CR) for newly diagnosed focal epilepsy. In the OLE study, all patients received ESL (800-1600 mg/d) for 2 years. Primary efficacy outcome was retention time (from baseline of the OLE study). Secondary efficacy assessments included seizure freedom rate (no seizures during the OLE study) and responder rate (≥50% seizure frequency reduction from baseline of double-blind trial). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs).

Results: Of 206 randomized patients, 96 who received ESL in the double-blind trial (ESL/ESL) and 88 who received CBZ-CR in the double-blind trial (CBZ-CR/ESL) were treated with ESL monotherapy (89.3% overall). Treatment retention time was similar between groups, with low probability of ESL withdrawal overall (<0.07 at any time). After 24 months, the probability of ESL withdrawal was 0.0638 (95% confidence interval [CI] = 0.0292-0.1366) in the ESL/ESL group and 0.0472 (95% CI = 0.0180-0.1210) in the CBZ-CR/ESL group. Seizure freedom rates were 90.6% (ESL/ESL) and 80.7% (CBZ-CR/ESL; P = .0531). Responder rates remained >80% in both groups throughout the study. Incidence of serious TEAEs was similar between groups (7.3% vs 5.7%; 0% vs 1.1% possibly related), as were the incidences of TEAEs considered at least possibly related to treatment (17.7% vs 18.2%) and TEAEs leading to discontinuation (3.1% vs 4.5%). The types of TEAEs were generally consistent with the known safety profile of ESL.

Significance: ESL monotherapy was efficacious and generally well tolerated over the long term, including in patients who transitioned from CBZ-CR monotherapy. No new safety concerns emerged.

Keywords: antiseizure medication; carbamazepine; focal seizures; responder rate; retention; seizure freedom rate.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anticonvulsants / therapeutic use*
  • Dibenzazepines / therapeutic use*
  • Double-Blind Method
  • Epilepsies, Partial / diagnosis*
  • Epilepsies, Partial / drug therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Anticonvulsants
  • Dibenzazepines
  • eslicarbazepine acetate