High Treatment Response Observed With Perampanel in Patients With Drug-Resistant Epilepsy

Infection-related epilepsy etiology, experiencing multiple types of seizures, and cognitive impairment were independent influencing factors on perampanel use retention.

In a newly published 6-month, single-center study, perampanel, a third-generation antiseizure medication (ASM), continued to demonstrate its efficacy in reducing seizure frequency for patients with drug-resistant epilepsy (DRE). The investigators concluded that this data provides a basis for evaluating the potential for expected efficacy and duration of use of perampanel when given as an additive treatment for this patient population.1

There have been numerous randomized controlled trials and real-world studies evaluating the efficacy of perampanel in patients with DRE; however, most studies examined adults and minors separately, whereas this analysis included patients across the lifespan. In this observational study, 47.2% (n = 34) of patients demonstrated a treatment response, which was within the range reported in previous RCT studies.

Senior author Yanan Chen, department of neurology, Zhengzhou University People’s Hospital, in Zhengzhou, China, and colleagues collected clinical data on 72 patients with DRE who were on perampanel for a mean duration of 10.6 months. In total, 27.8% of patients (n = 20) were minors and 72.2% (n = 52) were adults, with ages ranging from 10-62 years. Perampanel was added on to the ASMs for these patients and was administered orally at a starting dose of 2 mg/day at bedtime, titrated slowly, and increased by 1-2 mg every 2-4 weeks.

In total, 25% of patients (n = 18) were seizure-free and 22.2% (n = 16) demonstrated a treatment response at the 6-month follow-up. The remaining 38 patients had a nonresponse, including 8.3% (n = 6) who were too short on perampanel use due to adverse effects (AEs) and 2.8% (n = 2) of patients who had increased seizure activity.

READ MORE: Demographic and Clinical Variables of Drug-Resistant Epilepsy Associated With Modified Atkins Diet Initiation

On univariate analysis, treatment response was significantly lower among those who had baseline seizure frequency that exceeded 4 seizures/month (odds ratio [OR], 0.232; 95% CI, 0.077-0.702; P = .01). Additionally, investigators also observed statistically significant differences among those who did and did not previously fail 3 or more ASMs.

"Repeated seizures have been shown to produce neuronal loss and mossy fiber sprouting in the hippocampus, which in turn can reinforce their production forming excitatory recurrent circuits,” Chen and coinvestigators wrote. "This underlying mechanism may reduce the seizure inhibition effect of PER in patients with more seizures at baseline frequency. We speculate that these influencing factors may be relevant to other types of ASMs as well."

The retention rate of perampanel was 77.8%, with 16 patients withdrawing treatment. In addition to AEs, 8.3% (n = 6) of patients withdrew because of lack of efficacy, while 1 patient withdrew from a combination of AEs and lack of efficacy, and 1 patient from economic hardship.

According to the multifactorial Cox regression, patients with DRE caused by infection had lower retention rates than patients with DRE that were underwritten by noninfectious causes (OR, 15.957; 95% CI, 2.692-68.972; P <.001). Additionally, those with only 1 type of seizure (OR, 0.053; 95% CI, 0.006-0.476; P = .009) and patients with that weren’t cognitively impaired (OR, 134.253; 95% CI, 5.623-3205.1.04; P = .002) had longer durations of perampanel use.

The presence of absence of infection-related etiology, having more than 1 type of seizure, and the presence or absence of comorbid cognitive impairment were considered independent factors of perampanel use among patients with DRE. "We estimated that patients with DRE whose epilepsy was caused by infection-related etiology, patients with more than one type of seizure, and patients with comorbid cognitive impairment would have much shorter PER [perampanel] use duration than patients without these clinical characteristics," the study authors wrote.

REFERENCE
1. Zhang Y, Han X, Zhao P, et al. Perampanel add-on therapy for drug-refractory epilepsy: a single-center retrospective study based on 6-month treatment outcomes in central China. Published online February 23, 2022. doi:10.1016/j.yebeh.2022.108617