Perampanel as first add-on antiseizure medication: Italian consensus clinical practice statements

Bonanni, Paolo; Gambardella, Antonio; Tinuper, Paolo; Acone, Benedetto; Perucca, Emilio; Coppola, Giangennaro

doi:10.1186/s12883-021-02450-y

Cited by 10 publications

(6 citation statements)

References 52 publications

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“…Although retention and seizure freedom rates for total seizures did not differ significantly between the first and second add-on subgroups, responder rates for total seizures were significantly higher in the first vs. second add-on subgroup at Month 12 and the last visit, indicating that PER may be particularly effective in the first add-on setting. An Italian consensus clinical practice statement has already acknowledged that PER has many features that justify its use as a first add-on therapy ( 26 ), and, taken together, the findings of the current study provide evidence to support these recommendations. PER was particularly effective in PWE with GTCS, regardless of whether it was used as early or late add-on therapy, supporting its use as a broad-spectrum ASM ( 21 , 27 ).…”

Section: Discussionsupporting

confidence: 72%

Perampanel outcomes at different stages of treatment in people with focal and generalized epilepsy treated in clinical practice: Evidence from the PERMIT study

et al. 2023

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IntroductionThe PERMIT study is the largest pooled analysis of perampanel (PER) clinical practice data conducted to date.MethodsThis post-hoc analysis of PERMIT investigated the effectiveness, safety and tolerability of PER when used as early add-on therapy (after failure of one or two previous antiseizure medications) in comparison with late add-on therapy (after failure of three or more previous antiseizure medications). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness was assessed by seizure type (total seizures, focal seizures, generalized tonic-clonic seizures [GTCS]) and assessments included seizure freedom rate and responder rate. Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs.ResultsThe Full Analysis Set included 1184 and 2861 PWE treated with PER as early and late add-on therapy, respectively. Compared to the late add-on subgroup, the early add-on subgroup was characterized by later mean age at epilepsy onset, shorter mean duration of epilepsy, lower rates of intellectual disability and psychiatric comorbidity, and lower frequency of seizures per month, suggesting a less severe form of epilepsy in this subgroup. After 12 months, retention was significantly higher in the early versus late add-on subgroup (67.7% vs. 62.4%; p = 0.004). At the last visit, responder rates in the early versus late add-on subgroup were significantly higher for total seizures (68.2% vs. 39.3%; p < 0.001), focal seizures (65.0% vs. 36.8%; p < 0.001) and GTCS (83.7% vs. 67.2%; p < 0.001), as were seizure freedom rates (total seizures, 35.9% vs. 11.9% [p < 0.001]; focal seizures, 29.4% vs. 8.7% [p < 0.001]; GTCS, 69.0% vs. 48.1% [p < 0.001]). Incidence of AEs was significantly lower in the early versus late add-on subgroup (42.1% vs. 54.7%; p < 0.001), as was the rate of discontinuation due to AEs over 12 months (15.0% vs. 18.1%; p = 0.031).DiscussionThis study demonstrated that PER was effective and generally well tolerated when initiated as early or late add-on therapy, but it was significantly more effective and better tolerated when initiated early. These findings support PER's use as a broad-spectrum, early add-on therapy for use in PWE with focal and generalized seizures.

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Section: Discussionsupporting

confidence: 72%

Perampanel outcomes at different stages of treatment in people with focal and generalized epilepsy treated in clinical practice: Evidence from the PERMIT study

et al. 2023

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“…Behavioral and psychiatric side effects were frequently reported with PER treatment 26 . In fact, a total of 56 patients (16.5%) experienced mild or moderate AEs, particularly for irritability (17/56, 30.3%).…”

Section: Discussionmentioning

confidence: 99%

Effectiveness and safety of mono‐ and add‐on perampanel in pediatric patients with epilepsy: Experience from a single‐center retrospective study

Li,

Guo,

et al. 2023

Epilepsia Open

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ObjectiveTo evaluate the effectiveness and safety of perampanel (PER) monotherapy (MT) or add‐on therapy (AT) in Chinese children with epilepsy, as well as to evaluate the data from routine therapeutic drug monitoring (TDM) of PER for these pediatric patients.MethodsThis retrospective and observational study was carried out on children with epilepsy (n = 340) from 2020 to 2022 at the Children's Hospital of Nanjing Medical University. Outcome measures were the responder rate (50% or greater seizure reduction), long‐term efficacy, and tolerability (number and types of adverse events) in MT and AT groups. Concentrations of plasma PER obtained from these patients, if available, were analyzed too.ResultsA total of 279 patients achieved at least 3 months of therapy, and 58.1% responded to PER therapy. 53 of the responders were seizure‐free (32.7%). The retention rate dropped from 88.0% at 3 months to 40.6% at 12 months after treatment. Patients with MT achieved better seizure control than those with AT (P <0.001). Intriguingly, PER exerted a very weak effect on patients who took more than 2 ASMs or were diagnosed with drug‐resistant epilepsy. There were no significant differences in tolerability between the two groups. In addition, 179 patients were routinely monitored for PER, and the trough concentrations (C0) for these patients ranged from 30.0 to 992.0 ng/mL. However, no significant difference in C0 was observed between responders and nonresponders (333 ng/mL vs 325.5 ng/mL, P = 0.264).SignificanceThis study provides effectiveness and safety data on Chinese children with epilepsy treated with PER either as MT or as AT. The efficacy of patients receiving MT was much better than cases administered with more than 2 ASMs or diagnosed with drug‐resistant epilepsy. In addition, no association was found between the plasma PER concentration and efficacy or safety.

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“…Compromised cognitive function is a common effect associated with some ASMs 9 , 10 , 13 , 27 and cognitive deficits may negatively affect patients’ QoL, 47 , 48 which may in turn lead to treatment discontinuation. Although published data in this regard are lacking in elderly patients, evidence in adults has shown that the drug is not associated with significant cognitive AEs.…”

Section: Best Practice Expert Recommendationsmentioning

confidence: 99%

“…45 Perampanel's favorable effect on sleep architecture without worsening daytime sleepiness, 45 coupled with its indication to be taken before bedtime, 28 is likely to benefit patients who suffer from sleep disorders. 16,45,46 Cognitive AEs Compromised cognitive function is a common effect associated with some ASMs 9,10,13,27 and cognitive deficits may negatively affect patients' QoL, 47,48 which may in turn lead to treatment discontinuation. Although published data in this regard are lacking in elderly patients, evidence in adults has shown that the drug is not associated with significant cognitive AEs.…”

Section: Somnolence and Sleep Disordersmentioning

confidence: 99%

Optimal Use of Perampanel in Elderly Asian Patients with Epilepsy: Expert Opinion

Huang¹,

Boonyapisit²,

Gunadharma³

et al. 2022

TCRM

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Managing epilepsy in the elderly remains complicated largely due to factors related to aging. In this population, management practices are increasingly shifting towards the use of newer-generation anti-seizure medications (ASMs) as they are generally associated with better tolerability and safety profiles than older ones. Perampanel is a new ASM with broad-spectrum efficacy and a favorable safety profile. However, because of the lack of information and experience in its use, the prescription of perampanel has not been optimized in the elderly in the real-world setting in Asia. A group of epilepsy experts across the region convened at a series of virtual meetings to share their experience and discuss recommendations on perampanel use in elderly patients, including dose optimization, considerations with treatment initiation, and strategies to manage adverse events and maximize tolerability. This article summarizes key clinical and real-world evidence for perampanel in the elderly and consolidates the experts’ opinions on optimizing perampanel use in elderly Asian patients with epilepsy, providing practical guidance for clinicians to address challenges related to treatment initiation and tolerance.

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Perampanel as first add-on antiseizure medication: Italian consensus clinical practice statements

Cited by 10 publications

References 52 publications

Perampanel outcomes at different stages of treatment in people with focal and generalized epilepsy treated in clinical practice: Evidence from the PERMIT study

Perampanel outcomes at different stages of treatment in people with focal and generalized epilepsy treated in clinical practice: Evidence from the PERMIT study

Effectiveness and safety of mono‐ and add‐on perampanel in pediatric patients with epilepsy: Experience from a single‐center retrospective study

Optimal Use of Perampanel in Elderly Asian Patients with Epilepsy: Expert Opinion

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