Italy: Researchers have provided real-world evidence on perampanel (PER) effectiveness in managing Lennox-Gastaut syndrome (LGS) seizures. This study was published in Epilepsia. The lead researcher of this study is Sara Matricardi.
Lennox–Gastaut syndrome (LGS) is a developmental and epileptic encephalopathy (DEE) with onset between 18 months and eight years. The condition has a poor response to pharmacological and nonpharmacological therapies.

There needs to be more data and evidence on treatment. Valproate remains a primary therapeutic option. This study aimed to assess the long-term effectiveness of PER as an adjunctive treatment of seizures in a cohort of children and adults with LGS.
Time to PER failures (discontinuation/initiation of other treatment) and time to seizure relapse (seizure occurrence in seizure-free patients and increase of 50 % in average frequency of seizures) in responders were the primary outcomes measured in the study.
The study summary includes the following:
Researchers included Eighty-seven patients.
Fifty-two subjects had treatment failure constituting 59.8% of subjects at a median of 12 months.
Twenty-seven patients had a lack of efficacy, 14 had a lack of tolerability, and 11 had both reasons. This was the cause of Treatment failure constituting 52%, 27 % and 21 %, respectively.
A slower titration lowered the risk of PER failure than faster titration schedules.
There was an association between adverse events and an increased risk of treatment failure.
Thirty-six patients were responders in a follow-up of 11 months.
Seizure relapse occurred in 36.1% of patients after 21 months (median time).
At the end of the follow-up, the overall rate of seizure responders was 26.4%.
This study provides real-world evidence of the effectiveness of PER as adjunctive treatment in LGS patients.
The study strengths were recruitment at multiple sites, real-world design, treatment outcomes measured and increased generalizability of the results. Major limitations include open-label and retrospective design, lack of control group, and sources of bias.
Concluding further, PER is effective in LGS patients. It is well tolerated, and there is a possible partial loss of efficacy in a few patients over time.
They said, based on the findings of our study, PER is a valuable therapeutic option for LGS patients with inadequately controlled seizures.
They also mentioned that “we cannot draw firm conclusions on its usage as a first-line treatment.”
More information is required on the underlying pathophysiological mechanisms of LGS for a better-personalised approach and to develop disease-modifying treatments.
Further reading:
Long-term effectiveness of add-on perampanel in patients with Lennox–Gastaut syndrome: A multicenter retrospective study.
https://onlinelibrary.wiley.com/doi/10.1111/epi.17601