Newer antiepileptic drugs compared to levetiracetam as adjunctive treatments for uncontrolled focal epilepsy: An indirect comparison.

PURPOSE: Newer antiepileptic drugs (AEDs), such as Eslicarbazepine (ESL), Lacosamide (LAC), Perampanel (PER) and Brivaracetam (BRV), have been marketed as adjunctive treatments for partial-onset seizures. Our aim was to compare the efficacy and tolerability of newer AEDs with Levetiracetam (LEV), when used as add-on treatments for uncontrolled focal epilepsy.

METHOD: We conducted an online database search on PubMed, Embase, Cochrane Online Library and Clinicaltrials.gov for all available randomized controlled trials (RCTs) investigating the therapeutic effects of newer AEDs or LEV vs placebo. Indirect comparisons for clinical efficacy and tolerability at different doses between the newer AEDs and LEV were then performed using Indirect Treatment Comparison (ITC) software.

RESULTS: Twenty-four RCTs with a total of 8540 patients were included. Compared to LEV, ESL, LAC and BRV did not showed significant difference in efficacy at all dose level. PER showed lower 50% response rates and seizure-free rates at the highest effective recommended dosages. Treatment-emergent adverse events (TEAEs) and withdrawal rates due to adverse events (AEs) of LAC and PER were higher than LEV at the highest effective recommended dosages, and overall AE rates from ESL were higher than LEV.

CONCLUSIONS: Indirect comparisons suggested that ESL, LAC and BRV were not inferior to LEV in efficacy. ESL, LAC and PER may have a possible worse tolerability profile compared to LEV at high dose. But BRV may exhibit a similar tolerability to LEV. Newer AEDs cannot exceed the LEV on efficacy and tolerability.