(45) Safety and Efficacy of Perampanel in Epilepsy: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Saturday, August 27, 2022

8:00 AM – 6:00 PM CEST

Location: Hall C

Publication Number: 719

Presenting Author(s)

Alekhya Lavu
– The University of Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada

Co-Author(s)

Laila Nabil Mahmoud Helmy Aboulatta
– PhD student, University of Manitoba, Winnipeg, Manitoba, Canada
Ahamed M. abou-Setta
– George & Fay Yee Center for Healthcare Innovation, Winnipeg, Manitoba, Canada, Winnipeg, MB, Canada
Basma Aloud
– University of Manitoba, MB, Canada
Nicole Askin
– WRHA Virtual Library, University of Manitoba, Winnipeg, MB, Canada
Rasheda Rabbani
– George & Fay Yee Center for Healthcare Innovation, Winnipeg, Manitoba, Canada, MB, Canada
Walid Shouman
– University of Manitoba, Winnipeg, MB, Canada
Ryan Zarychanski
– Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada, Canada
Sherif Eltonsy, PhD
– Assistant Professor, University of Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada

Background: Perampanel is a third-generation antiepileptic drug prescribed for seizure control in epilepsy patients. Previous reviews have reported better seizure control and seizure freedom with perampanel compared with placebo. With additional randomized controlled trials (RCTs) available, there is a need for an updated review.

Objectives: The main objective of this study is to identify, critically appraise, and summarize the evidence on the efficacy and safety of perampanel in epilepsy.

Methods: This review included RCTs on patients with epilepsy (all seizure types) exposed to perampanel. Placebo or one or more pre-existing antiepileptic drugs before randomization were used as the comparison group. Electronic databases including MEDLINE (OVID), EMBASE (OVID), Cochrane Central Register of Controlled Trials (OVID), IPA (OVID), and trial registries, including ClinicalTrials.gov and International Clinical Trials Registry Platform (ICTRP), were searched to find relevant citations from inception to July 2021. No language or age restrictions were applied. Included outcomes were 50% responder rate, 100% seizure-free rate, discontinuation due to treatment-emergent adverse events (TEAE)s, having any TEAEs, and most reported TEAEs. We pooled results using random-effects models, reporting risk ratios (RR) and 95% confidence intervals (CI). The Cochrane risk of bias tool in Revan 5.4 was used to evaluate the included RCT's risk of bias (ROB).

Results: From 2211 retrieved citations, eight RCTs met our inclusion criteria. The 50% responder and 100% seizure freedom rates were significantly higher in patients receiving perampanel when compared to placebo (RR 1.57, 95 % CI 1.35 to 1.82, I215% and RR 2.79, 95% CI 1.58 to 4.93, I27% respectively). Discontinuations were also significantly higher for perampanel compared to placebo (RR 2.22, 95% CI 1.54 to 3.22, I2 0%, 6 RCTs). Compared with placebo, both 8mg and 12mg doses of perampanel showed similar efficacy in seizure control; however, a higher risk of treatment discontinuation was found among 12mg users. Dizziness, somnolence, and headache were the most commonly reported TEAEs in all the included trials. A higher percentage of patients reporting dizziness was observed with the increase in the perampanel dose.

Conclusions: This systematic review reports a significant reduction in seizures and a potential dose-dependent increase in discontinuations due to TEAE. Further larger and independent RCTs studying the most effective and safe dose of perampanel are needed.