OBJECTIVE: To assess the efficacy and safety of eslicarbazepine acetate (ESL) monotherapy. METHODS: This post hoc pooled analysis of 2 randomized double-blind studies (093-045 and -046) included adults with partial-onset seizures medically uncontrolled by 1 or 2 antiepileptic drugs (AEDs). Following the baseline period (8 weeks), eligible patients were randomized 2:1 to receive ESL 1,600 mg or 1,200 mg once daily for 18 weeks; the primary endpoint was study exit by meeting predefined exit criteria (signifying worsening seizure control). In each study, treatment was considered effective if the upper 95% confidence limit for exit rate was lower than the historical control threshold (65.3%). RESULTS: Pooled exit rates were as follows: ESL 1,600 mg = 20.6% (95% confidence interval: 15.6%-26.8%); ESL 1,200 mg = 30.8% (23.0%-40.5%). Use of 2 baseline AEDs or rescue medication, US location, epilepsy duration ≥20 years, and higher maximum baseline seizure frequency were associated with higher exit risks. Median percent reductions in standardized seizure frequency between baseline and the 18-week double-blind period were as follows: ESL 1,600 mg = 43.2%; ESL 1,200 mg = 35.7%; baseline carbamazepine use was associated with smaller reductions. Safety profiles were similar between ESL doses. CONCLUSIONS: Exit rates for ESL monotherapy (1,600 mg and 1,200 mg once daily) were lower than the historical control threshold, irrespective of baseline AED use and region, with no additional safety concerns identified. Clinical factors and location clearly influence treatment responses in conversion-to-monotherapy trials. CLASSIFICATION OF EVIDENCE: This pooled analysis provides Class IV evidence that for adults with medically uncontrolled partial-onset seizures, ESL monotherapy is well tolerated and effective.

From Thomas Jefferson University Marlborough MA

Zobrazit více v PubMed

Perucca E. Designing clinical trials to assess antiepileptic drugs as monotherapy. CNS Drugs 2008;22:917–938. PubMed

Perucca E, Tomson T. The pharmacological treatment of epilepsy in adults. Lancet Neurol 2011;10:446–456. PubMed

Hebeisen S, Pires N, Loureiro AI, et al. Eslicarbazepine and the enhancement of slow inactivation of voltage-gated sodium channels: a comparison with carbamazepine, oxcarbazepine and lacosamide. Neuropharmacology 2015;89:122–135. PubMed

Sperling MR, Harvey J, Grinnell T, Cheng H, Blum D; 045 Study Team. Efficacy and safety of conversion to monotherapy with eslicarbazepine acetate in adults with uncontrolled partial-onset seizures: a randomized historical-control phase III study based in North America. Epilepsia 2015;56:546–555. PubMed PMC

Jacobson MP, Pazdera L, Bhatia P, et al. Efficacy and safety of conversion to monotherapy with eslicarbazepine acetate in adults with uncontrolled partial-onset seizures: a historical-control phase III study. BMC Neurol 2015;15:46. PubMed PMC

Commission on Classification and Terminology of the International League Against Epilepsy (ILAE). Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 1981;22:489–501. PubMed

WHO Collaborating Centre for Drug Statistics Methodology. ATC/DDD index. Available at: http://www.whocc.no/atc_ddd_index/. Accessed October 23, 2015.

French JA, Wang S, Warnock B, Temkin N. Historical control monotherapy design in the treatment of epilepsy. Epilepsia 2010;51:1936–1943. PubMed

U.S. Food and Drug Administration. Ling X. Lamictal® XR™ (lamotrigine) historical-controlled trial: Peripheral and Central Nervous System Drugs Advisory Committee Meeting 2011. Available at: http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/peripheralandcentralnervoussystemdrugsadvisorycommittee/ucm247490.pdf. Accessed October 23, 2015.

Wechsler RT, Li G, French J, et al. Conversion to lacosamide monotherapy in the treatment of focal epilepsy: results from a historical-controlled, multicenter, double-blind study. Epilepsia 2014;55:1088–1099. PubMed PMC

Fisher RS, Acevedo C, Arzimanoglou A, et al. A practical clinical definition of epilepsy. Epilepsia 2014;55:475–482. PubMed