Abstracts

Rationale: Use of antiepileptic drugs (AEDs) may increase the risk of falls and fractures (Ahmad et al. Neurology 2012;79:145-51). Eslicarbazepine acetate (ESL) is a once-daily (QD) oral AED, approved in the US and EU as adjunctive treatment of partial-onset seizures (POS). This post-hoc analysis of three phase III trials of adjunctive ESL for POS assessed the incidence of falls, fractures, and injuries in patients who received ESL, compared with those who received placebo. Methods: A post-hoc analysis of pooled data from three phase III studies (BIA-2093-301/-302/-304) was performed. Patients were aged ≥16 years, with ≥4 POS/month, receiving 1-3 AEDs. After an 8-week baseline period, patients were randomized equally to receive placebo or ESL 400mg (2 studies), 800mg, or 1200mg QD for 14 weeks (including a 2-week titration period). The incidences of falls, fractures, and injuries (including head injuries) were analyzed and compared with seizure diary records, clinical database data and safety narratives, to determine whether or not these events were related to seizures or, in the case of fractures and injuries, to seizures or falls. A fall, fracture, or injury was attributed to a seizure/fall if it occurred ≤3 days after the event. Complex partial, unclassified and secondarily generalized seizures, but not simple partial seizures were considered in this analysis. Results: A total of 426 placebo-treated and 1021 ESL-treated patients were included in this analysis. The median patient age was 37.0-38.0 years; approximately 80% of patients were Caucasian and 72% were taking ≥2 concomitant AEDs. The overall incidence of any falls, fractures, and injuries (including head injuries) was <10%, and was similar for the ESL 400mg, 800mg, and 1200mg groups (5.1%, 9.4%, and 5.1%), and the placebo group (6.1%); incidence did not increase with increasing ESL dose (Table 1). In this category of treatment-emergent adverse events, those reported most frequently were falls, contusions, and head injuries (all <2%). Concomitant use of carbamazepine did not affect the frequency of falls or contusions. In both the placebo and ESL groups, most (>50%) falls, fractures, and injuries (including head injuries) were related to seizures. Only one third of fracture events were related to falls. Conclusions: The incidence of falls, fractures, and injuries was low (<10%), was similar between the ESL and placebo groups, and did not increase with increasing ESL dose. The majority of falls, fractures, and injuries (including head injuries) were related to seizures.