Clinical factors associated with perampanel retention, response, seizure freedom and tolerability: real-world evidence from the PERMIT Extension study

Background: Perampanel (PER) is effective in treating focal and generalised seizures. The PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) Extension study was a large, pooled analysis of PER clinical practice studies that assessed the effectiveness and safety/tolerability of PER in over 6800 people with epilepsy. Objectives: To determine clinical factors associated with PER retention, response, seizure freedom and tolerability when used in clinical practice. Design: An exploratory post hoc analysis of data from all individuals included in PERMIT Extension. Methods: Univariate and multivariable logistic regression analyses were performed to identify baseline factors associated with retention rate, responder rate (⩾50% seizure frequency reduction), seizure freedom rate (no seizures since at least the previous visit) and incidence of adverse events (AEs). Results: A total of 6822 people with epilepsy treated with PER were included. Baseline factors associated with retention were absence of psychiatric comorbidity (odds ratio [95% confidence interval], 1.99 [1.403–2.825]; p < 0.001), fewer focal seizures (1.01 [1.004–1.014]; p < 0.001) and fewer previous antiseizure medications (ASMs; 1.06 [1.013–1.119]; p = 0.013). Factors associated with response were absence of focal seizures (2.12 [1.532–2.924]; p < 0.001), fewer previous ASMs (1.19 [1.136–1.250]; p < 0.001) and absence of concomitant sodium channel blocker (SCB) ASM(s) (1.96 [1.455–2.628]; p < 0.001). Factors associated with seizure freedom were fewer total seizures (1.04 [1.020–1.061]; p < 0.001), absence of focal seizures (3.45 [2.387–4.979]; p < 0.001), fewer previous ASMs (1.11 [1.028–1.205]; p = 0.008), absence of concomitant SCB ASM(s) (1.46 [1.051–2.028]; p = 0.024) and absence of concomitant gamma-aminobutyric acid (GABA)-ergic ASM(s) (2.08 [1.266–3.412]; p = 0.004). Factors associated with occurrence of AEs were older age (1.01 [1.006–1.015]; p < 0.001), longer epilepsy duration (1.01 [1.010–1.012]; p = 0.044), presence of psychiatric comorbidity (1.74 [1.469–2.062]; p < 0.001) and greater number of previous ASMs (1.09 [1.069–1.119]; p < 0.001). Conclusion: This study identified clinical factors associated with PER’s real-world effectiveness and tolerability, which may help inform treatment decisions in clinical practice.