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

Trinka E.; Rocamora R.; Chaves J.; Moreira J.; Ikedo F.; Soares-da-Silva P.; Estol C.; Newton M.; Carne R.; Kowacs P.; Petrova D.; Syankov D.; Maslarov D.; Stanev S.; Lasso J.; Bašić S.; Bar M.; Vyskočilová D.; Pazdera L.; Haldre S.; Kaarina Kälviäinen R.; Peltola J.; Georges Maillard L.; Deckert-Schmitz M.; Springub J.; Barcs G.; Ménes A.; Tóth M.; Giallonardo A.T.; Paganini M.; Asmane S.; Logina L.; Meilute Lescinskiene L.; Cruz A.; Umeres H.; Czapiński P.; Trzebińska-Frydrychowska E.; Sales F.; Falup-Pecurariu C.G.; Silviu Manescu E.; Roceanu A.-M.; Odinak M.; Tretyakova E.; Volkova L.; Lebedeva A.; Lipatova L.; Bogdanov E.; Vladimirovna Polezhaeva T.; Gebauer-Bukurov K.; Jovanovic-Mihajlovic N.; Milovanovic M.; Spasic M.; Lipovský L.; Perichtová M.; Chamilová J.; Balaguer E.; Ugarte A.; Dubenko A.; Kharchuk S.; Moroz S.; Shkrobot S.; Mar'yenko L.; Litovchenko T.; Cock H. · Epilepsia (2020) · DOI: 10.1111/epi.16666

Resumen

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.