Steve Chung1, Saurabh R Sinha2, Aashit Shah3, John M Stern4, Hailong Cheng5, JungAh Jung5, Todd Grinnell5, David Blum5. 1. Banner University Medical Center, 755 E. McDowell Road, Phoenix, AZ, 85006, USA. Electronic address: Steve.Chung@bannerhealth.com. 2. Duke University Medical Center, Box 102350, Durham, NC, 27710, USA. 3. Carilion Clinic, Virginia Tech Carilion School of Medicine, 3 Riverside Circle, Roanoke, VA, 24016, USA. 4. Department of Neurology, UCLA Medical Center, 710 Westwood Plaza, Suite 1250, Los Angeles, CA, 90095, USA. 5. Sunovion Pharmaceuticals Inc., 84 Waterford Drive, Marlborough, MA, 01752, USA.
Abstract
OBJECTIVE: To assess the long-term safety and efficacy of eslicarbazepine acetate (ESL) monotherapy in adults with focal seizures (FS). METHODS: Study 050 was a long-term, multicenter, open-label (OL) safety extension of two conversion-to-ESL monotherapy studies in adults with refractory FS. After participating in Study 045 or 046, patients started on ESL 1600 mg once daily (QD) (or 1200 mg if they previously had a dose reduction), and could adjust the dose 400 mg/week to a dose between 800-2400 mg QD. Patients could add up to two additional antiepileptic drugs (AEDs). This post-hoc analysis focuses on the actual monotherapy subgroup, which included patients in Studies 045/046/050 who did not add additional AEDs. Study endpoints included treatment retention time, time on ESL monotherapy, change in standardized seizure frequency (SSF), change in quality of life (QoL) in epilepsy (QOLIE-31) and Montgomery-Åsberg Depression Rating Scale (MADRS) scores, and incidence of treatment-emergent adverse events (TEAEs); serious adverse events (SAEs), TEAEs leading to discontinuation, and TEAEs related to allergic reaction, hyponatremia and thyroid function were also evaluated. RESULTS: There were 274 patients in the Study 050 full intent-to-treat (ITT) population and 140 patients in the actual monotherapy subgroup. Median treatment retention time and time on ESL monotherapy were both >5 years. Median reduction in SSF from baseline was 66.4% in the full ITT population and 78.3% in the actual monotherapy subgroup; responder (≥50% reduction in SSF) rates were 62.4% and 74.3%, respectively. QOLIE-31 scores increased from baseline in the full ITT population and the actual monotherapy subgroup (4.1- and 7.5-point increases, respectively). MADRS scores decreased from baseline in both the full ITT population and the actual monotherapy subgroup (0.7- and 2.9-point decreases, respectively). TEAEs occurred in 85.4% of patients in the full ITT population and 81.4% of patients in the actual monotherapy subgroup. Incidences of SAEs and TEAEs leading to discontinuation, as well as dizziness, depression, fall, partial seizures with secondary generalization, and complex partial seizures, were higher in the full ITT population than in the actual monotherapy subgroup. Allergic reactions, hyponatremia, and hypothyroidism were infrequent, particularly in the actual monotherapy subgroup. CONCLUSIONS: The results of this post-hoc analysis suggest that long-term treatment with ESL was effective and well tolerated, both as a monotherapy and in combination with other AEDs for FS. QoL and tolerability appeared to be better, and incidence of depression lower, in the patient population taking ESL as a monotherapy, compared with the population that included patients taking ESL as an adjunctive therapy.
RCT Entities:
OBJECTIVE: To assess the long-term safety and efficacy of eslicarbazepine acetate (ESL) monotherapy in adults with focal seizures (FS). METHODS: Study 050 was a long-term, multicenter, open-label (OL) safety extension of two conversion-to-ESL monotherapy studies in adults with refractory FS. After participating in Study 045 or 046, patients started on ESL 1600 mg once daily (QD) (or 1200 mg if they previously had a dose reduction), and could adjust the dose 400 mg/week to a dose between 800-2400 mg QD. Patients could add up to two additional antiepileptic drugs (AEDs). This post-hoc analysis focuses on the actual monotherapy subgroup, which included patients in Studies 045/046/050 who did not add additional AEDs. Study endpoints included treatment retention time, time on ESL monotherapy, change in standardized seizure frequency (SSF), change in quality of life (QoL) in epilepsy (QOLIE-31) and Montgomery-Åsberg Depression Rating Scale (MADRS) scores, and incidence of treatment-emergent adverse events (TEAEs); serious adverse events (SAEs), TEAEs leading to discontinuation, and TEAEs related to allergic reaction, hyponatremia and thyroid function were also evaluated. RESULTS: There were 274 patients in the Study 050 full intent-to-treat (ITT) population and 140 patients in the actual monotherapy subgroup. Median treatment retention time and time on ESL monotherapy were both >5 years. Median reduction in SSF from baseline was 66.4% in the full ITT population and 78.3% in the actual monotherapy subgroup; responder (≥50% reduction in SSF) rates were 62.4% and 74.3%, respectively. QOLIE-31 scores increased from baseline in the full ITT population and the actual monotherapy subgroup (4.1- and 7.5-point increases, respectively). MADRS scores decreased from baseline in both the full ITT population and the actual monotherapy subgroup (0.7- and 2.9-point decreases, respectively). TEAEs occurred in 85.4% of patients in the full ITT population and 81.4% of patients in the actual monotherapy subgroup. Incidences of SAEs and TEAEs leading to discontinuation, as well as dizziness, depression, fall, partial seizures with secondary generalization, and complex partial seizures, were higher in the full ITT population than in the actual monotherapy subgroup. Allergic reactions, hyponatremia, and hypothyroidism were infrequent, particularly in the actual monotherapy subgroup. CONCLUSIONS: The results of this post-hoc analysis suggest that long-term treatment with ESL was effective and well tolerated, both as a monotherapy and in combination with other AEDs for FS. QoL and tolerability appeared to be better, and incidence of depression lower, in the patient population taking ESL as a monotherapy, compared with the population that included patients taking ESL as an adjunctive therapy.