Long-term Tolerability of Lacosamide and Controlled-release Carbamazepine Monotherapy by Number of Additional Medical Conditions: A Post Hoc Analysis (S3.008)

Objective: To assess the long-term tolerability of lacosamide (LCM) and carbamazepine controlled-release (CBZ-CR) monotherapy in adults with newly diagnosed epilepsy by number of comorbid conditions. Background: People with epilepsy have a higher prevalence of comorbid conditions than the general population. The presence of comorbid conditions may complicate epilepsy management and treatment. Design/Methods: Post hoc analysis of pooled data from SP0993 (NCT01243177) and the double-blind extension (SP0994; NCT01465997). SP0993 enrolled adults (≥16 years) with newly diagnosed epilepsy (focal or generalized tonic-clonic seizures). LCM and CBZ-CR were initiated at 100mg/day or 200mg/day, respectively, and titrated to a target dose of 200mg/day (LCM) or 400mg/day (CBZ-CR), with increases to 400/600mg/day (LCM) and 800/1200mg/day (CBZ-CR), if needed. Patient subgroups were based on the number of comorbid conditions at the Screening Visit (0, 1–2, ≥3). Outcomes of interest included drug-related treatment-emergent adverse events (TEAEs) and discontinuations due to TEAEs for each subgroup. Results: Of 886 patients treated in the combined trials (LCM: 444; CBZ-CR: 442), 245 patients (27.7%) had no comorbid conditions, 305 (34.4%) had 1–2 comorbid conditions, and 336 (37.9%) had ≥3 comorbid conditions. The incidence of drug-related TEAEs and discontinuations due to TEAEs increased by number of comorbid conditions, which was less pronounced in patients on LCM (overall drug-related TEAEs: LCM 40.8%, CBZ-CR 50.2%; discontinuations due to TEAEs: LCM 13.1%, CBZ-CR 19.0%). These findings were supported by the Kaplan-Meier estimated proportions of patients that did not discontinue treatment due to TEAEs at 1 and 2 years. Conclusions: Data from this post hoc analysis suggest an increased incidence of drug-related TEAEs and discontinuations due to TEAEs with higher number of comorbid conditions, which was less pronounced with LCM vs CBZ-CR monotherapy. These results may help clinicians determine appropriate treatment approaches for their patients with epilepsy and comorbid conditions. Disclosure: Dr. Ben-Menachem has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai, Sandoz, UCB. Dr. Ben-Menachem has received personal compensation in an editorial capacity for Acta Neurologica Scandinavica-Wiley Press. Dr. Ben-Menachem has received research support from Eisai, UCB, GW Pharma, SK Life Science. Dr. Grebe has nothing to disclose. Dr. Terada has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with UCB Japan, Eisai, Otsuka pharmaceutical, and Daiichi-Sankyo. Dr. Jensen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with UCB Pharma. Dr. Li has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with UCB Pharma. Dr. De Backer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with UCB Pharma. Dr. Gasalla has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with UCB Pharma. Dr. Gasalla holds stock and/or stock options in UCB Pharma. Dr. Brock has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with UCB. Dr. Biton has nothing to disclose.