Efficacy and tolerability of adjuvant perampanel: an Australian multicenter real-world observational study in refractory focal and generalized epilepsy syndromes

Parveen Sagar, Olivia Wawryk, Sara Vogrin, Emma Whitham, Michelle Kiley, Joseph Frasca, Ross Carne, Udaya Seneviratne, Mark J. Cook, Nicholas Lawn, Armin Nikpour, Wendyl Jude D'Souza

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Abstract

PURPOSE: To explore the efficacy and tolerability of adjuvant perampanel (PER) and their associated risk factors in late add-on drug-resistant epilepsy. METHOD: Retrospective multicenter 'real-world' observational study. Consecutively identified patients commenced on PER, with mixed epilepsy syndromes, from nine Australian epilepsy centers. Primary efficacy endpoints were at least 50% reduction in seizure frequency (responders), seizure freedom, and retention at 6 and 12 months, following a 3-month titration period. Tolerability endpoints were cessation of PER for any reason, cessation of PER due to treatment-emergent adverse events (TEAE), or cessation due to inefficacy. Outcomes were assessed for a-priori risk factors associated with efficacy and tolerability. RESULTS: Three-hundred and eighty seven adults were identified and followed up for a median of 12.1 months (IQR 7.0-25.2). Focal epilepsy accounted for 79.6% (FE), idiopathic generalized epilepsy (IGE), 10.3% and developmental epileptic encephalopathy (DEE) 10.1%, of the cohort. All patients had drug-resistant epilepsy, 71.6% had never experienced six months of seizure freedom, and the mean number of antiepileptic medications (AEDs) prior to starting PER was six. At 12 months, with missing cases classified as treatment failure, retention was 40.0%, responder 21.7%, and seizure freedom 9.0%, whereas, using last outcome carried forward (LOCF), responder and seizure freedom rates were 41.3% and 14.7%, respectively. Older age of epilepsy onset was associated with a marginal increase in the likelihood of seizure freedom at 12-month maintenance (OR 1.04, 95% CI 1.02, 1.06). Male sex (adjusted OR [aOR] 2.06 95% CI 1.33, 3.19), lower number of prior AEDs (aOR 0.84, 95% CI 0.74, 0.96) and no previous seizure-free period of at least 6-month duration (aOR 2.04 95% CI 1.21, 3.47) were associated with retention. Perampanel combined with a GABA receptor AED was associated with a lower responder rate at 12 months but reduced cessation of PER. The most common TEAEs were neuropsychiatric (18.86%), followed by dizziness (13.70%), and sleepiness (5.68%). CONCLUSIONS: Adjuvant PER treatment, even in late-add on drug-resistant epilepsy is an effective and well-tolerated treatment for drug-resistant epilepsy.

Original languageEnglish
Pages (from-to)107935
Number of pages1
JournalEpilepsy & Behavior
Volume119
DOIs
Publication statusPublished - 1 Jun 2021
Externally publishedYes

Keywords

  • Adjuvant perampanel refractory epilepsy
  • Drug resistant epilepsy
  • Perampanel efficacy
  • Real world studies
  • Retention
  • Tolerability

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