Effectiveness and safety of perampanel by concomitant antiseizure medications: Insights from the real-world PERMIT Extension study

The PERMIT Extension study is the largest pooled analysis of perampanel (PER) clinical practice data to date. A post-hoc analysis of PERMIT Extension assessed the effectiveness and tolerability of PER with different concomitant antiseizure medication (ASM) regimens. Effectiveness was assessed by evaluating responder and seizure freedom rates at the last observation for each participant ('last visit'), and tolerability was assessed by evaluating adverse events. The analysis included 5144 people with epilepsy who had only focal (n = 4347) or only generalised (n = 797) seizures when PER was initiated, and whose type of concomitant ASM regimen at that time was known. Effectiveness and tolerability varied considerably depending on the pharmacology and mechanism of action (MoA) of concomitant ASM regimens. For example, in individuals with focal seizures receiving only one concomitant ASM at baseline, seizure freedom rates were significantly higher if the concomitant ASM was one that binds to synaptic vesicle glycoprotein 2A (SV2A) versus one that does not bind to SV2A (41.7 % vs. 24.8 %; p < 0.001), and significantly lower if the concomitant ASM was a sodium channel blocker versus a non-sodium channel blocker (23.2 % vs. 35.6 %; p < 0.001); whereas, in those with generalised seizures receiving one concomitant ASM at baseline, there were no significant differences in seizure freedom rates according to the concomitant ASM's MoA. In individuals with focal and generalised seizures, tolerability appeared to be less affected by the pharmacology and MoA of concomitant ASM regimens. The findings from this study may help inform the use of rational polytherapy in clinical practice.