Abstracts

Rationale: People with epilepsy have a higher prevalence of medical comorbid conditions than the general population, which may complicate epilepsy management and treatment. This post-hoc analysis assessed the tolerability of lacosamide (LCM) and controlled-released carbamazepine (CBZ-CR) monotherapy by number of additional medical conditions in adults with newly diagnosed epilepsy. Methods: Adults (≥16 years) with newly diagnosed epilepsy (focal or generalized tonic-clonic seizures [without clear focal origin]) were enrolled in a double-blind, non-inferiority monotherapy trial (SP0993; NCT01243177) assessing the efficacy and tolerability of LCM vs CBZ-CR. LCM and CBZ-CR were initiated at 100mg/day or 200mg/day, respectively and were titrated to an initial target dose of 200mg/day (LCM) or 400mg/day (CBZ-CR). Depending on seizure control, doses could be increased to 400/600mg/day (LCM) and 800/1200mg/day (CBZ-CR). The incidence of treatment emergent adverse events (TEAEs), drug-related TEAEs and TEAEs leading to discontinuation were assessed in patients with 0, 1-2 and 3+ additional medical conditions (MedDRA, Version16.1) ongoing at the Screening Visit. Results: Of 886 patients receiving trial medication, 245 (27.7%) did not report any additional medical condition (LCM 122; CBZ-CR 123); 305 (34.4%) reported 1-2 (LCM 157; CBZ-CR 148) and 336 (37.9%) reported 3+ (LCM 165; CBZ-CR 171) additional medical conditions (Table 1). The mean number of comorbid conditions was 1.4 and 5.7 in patients with 1-2 and 3+ additional conditions, respectively. The most frequently reported medical condition was hypertension (15.1% and 44.9% in the 1-2 and 3+ subgroups, respectively). The majority of the patients were on the lowest target dose in all subgroups (range: LCM 68.8%-72.1%; CBZ 69.6%-79.7%). The proportion of patients with 0, 1-2 or 3+ additional medical conditions who reported at least one TEAE was 65.6%, 75.2% and 78.8% on LCM and 59.3%, 77.0% and 84.8% on CBZ-CR (Figure 1). Of the most frequently reported TEAEs (≥10% any subgroup), fatigue (LCM, CBZ-CR), headache (CBZ-CR), dizziness (CBZ-CR), and GGT increase (CBZ-CR) increased in incidence as the number of comorbid conditions increased. The proportion of patients with 0, 1-2 or 3+ additional medical conditions reporting at least one drug-related TEAE was 28.7%, 38.9% and 41.8% on LCM and 33.3%, 46.6% and 54.4% on CBZ-CR, and those discontinuing treatment due to TEAEs were 9.0%, 9.6% and 12.7% on LCM and 8.9%, 14.2% and 21.6% on CBZ-CR, respectively. Conclusions: The data from this post-hoc analysis suggest increased incidence of TEAEs, drug-related TEAEs and discontinuations due to TEAEs with higher number of comorbid medical conditions, which was less pronounced with LCM vs CBZ-CR monotherapy. In patients with ≥3 comorbid medical conditions, fewer patients on LCM reported drug-related TEAEs or discontinued treatment due to TEAEs compared with CBZ-CR. Funding: UCB Pharma-sponsored