Effectiveness of perampanel as the only add‐on: Retrospective, multicenter, observational real‐life study on epilepsy patients

Gasparini, Sara; Ferlazzo, Edoardo; Neri, Sabrina; Cianci, Vittoria; Iudice, Alfonso; Bisulli, Francesca; Bonanni, Paolo; Caggia, Emanuele; D’Aniello, Alfredo; Bonaventura, Carlo Di; DiFrancesco, Jacopo C.; Domina, Elisabetta; Gambardella, Antonio; Marini, Carla; Marrelli, Alfonso; Matricardi, Sara; Morano, Alessandra; Paladin, Francesco; Renna, Rosaria; Striano, Pasquale; Pascarella, Angelo; Ascoli, Michele; Aguglia, Umberto

doi:10.1002/epi4.12649

Cited by 10 publications

(10 citation statements)

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“…Retention, responder and seizure freedom rates were similar between subgroups with the exception of the ≥50% responder rate (66 vs. 53%; p = 0.05) and the seizure freedom rate (42 vs. 25%; p = 0.005) at 3 months, both significantly higher in the early vs. late add-on subgroup ( 52 ). The most frequently reported AEs were dizziness/vertigo and behavioral changes at all timepoints ( 52 ). Finally, a single-center, open-label study compared the efficacy of PER in individuals with a diagnosis of mesial temporal lobe epilepsy when used as first add-on therapy (due to inefficacy of a first ASM; n = 20) vs. late add-on therapy (due to inefficacy of ≥2 ASMs; n = 17) ( 53 ).…”

Section: Discussionmentioning

confidence: 85%

“…In both FAME and COM-PER, PER was shown to be particularly effective in PWE with FBTCS ( 49 , 51 ). In the clinical practice setting, a retrospective, observational, multicentre, longitudinal study assessed the effectiveness and tolerability of PER at 3, 6 and 12 months when used as the only add-on to ASM monotherapy in PWE with focal and generalized epilepsy aged >12 years ( 52 ) and a subanalysis was conducted to compare the use of PER as an early single add-on (after 0 or 1 previous add-on therapies) or late single add-on (after ≥2 previous add-on therapies) ( 52 ). Retention, responder and seizure freedom rates were similar between subgroups with the exception of the ≥50% responder rate (66 vs. 53%; p = 0.05) and the seizure freedom rate (42 vs. 25%; p = 0.005) at 3 months, both significantly higher in the early vs. late add-on subgroup ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

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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“…26 The final study was an Italian, multicenter, observational, retrospective study, in which PER was shown to be effective and well tolerated as only add-on therapy in 503 PWE with focal, generalized, or undetermined epilepsy treated for up to 12 months, although outcomes were not reported separately for PWE with generalized epilepsy. 27 No ASM has class I or II evidence of efficacy as initial monotherapy in people with IGE, 33 and treatment options are currently limited. Certain ASMs-particularly sodium channel blockers, such as carbamazepine, phenytoin, and in some instances also lamotrigine-can worsen seizure control in IGE and/or precipitate absence or myoclonic status epilepticus.…”

Section: F I G U R Ementioning

confidence: 99%

“…17,18 Clinical practice studies provide evidence on how a drug performs when used outside the relative restrictions of clinical trials, [19][20][21] but real-world evidence on the use of PER to specifically treat IGE is currently limited. [22][23][24][25][26][27] The PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) study included approximately 5200 people with focal and generalized epilepsy who were treated with PER in clinical practice. 28 The purpose of this study was to assess the real-world effectiveness and safety/ tolerability of PER when used to treat people with IGE included in PERMIT.…”

Section: Introductionmentioning

confidence: 99%

“…Approval of PER for the treatment of GTCS in IGE was based on the results of one phase 3, randomized, double‐blind, placebo‐controlled trial 17,18 . Clinical practice studies provide evidence on how a drug performs when used outside the relative restrictions of clinical trials, 19–21 but real‐world evidence on the use of PER to specifically treat IGE is currently limited 22–27 …”

Section: Introductionmentioning

confidence: 99%

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Perampanel for the treatment of people with idiopathic generalized epilepsy in clinical practice

Trinka

Alsaadi²,

Goji

et al. 2023

Epilepsia

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ObjectiveThis study was undertaken to evaluate perampanel (PER) when used under real‐world conditions to treat people with idiopathic generalized epilepsy (IGE) included in the PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) study.MethodsThe multinational, retrospective, pooled analysis PERMIT explored the use of PER in people with focal and generalized epilepsy treated in clinical practice across 17 countries. This subgroup analysis included PERMIT participants with IGE. Time points for retention and effectiveness measurements were 3, 6, and 12 months (last observation carried forward, defined as "last visit," was also applied to effectiveness). Effectiveness was evaluated by seizure type (total seizures, generalized tonic–clonic seizures [GTCS], myoclonic seizures, absence seizures) and included ≥50% responder rate and seizure freedom rate (defined as no seizures since at least the previous visit). Safety/tolerability was monitored throughout PER treatment and evaluated by documenting the incidence of adverse events (AEs), including psychiatric AEs and those leading to treatment discontinuation.ResultsThe Full Analysis Set included 544 people with IGE (51.9% women, mean age = 33.3 years, mean epilepsy duration = 18.1 years). At 3, 6, and 12 months, 92.4%, 85.5%, and 77.3% of participants were retained on PER treatment, respectively (Retention Population, n = 497). At the last visit, responder and seizure freedom rates were, respectively, 74.2% and 54.6% (total seizures), 81.2% and 61.5% (GTCS), 85.7% and 66.0% (myoclonic seizures), and 90.5% and 81.0% (absence seizures) (Effectiveness Population, n = 467). AEs occurred in 42.9% of patients and included irritability (9.6%), dizziness/vertigo (9.2%), and somnolence (6.3%) (Tolerability Population, n = 520). Treatment discontinuation due to AEs was 12.4% over 12 months.SignificanceThis subgroup analysis of the PERMIT study demonstrated the effectiveness and good tolerability of PER in people with IGE when administered under everyday clinical practice conditions. These findings are in line with clinical trial evidence, supporting PER's use as broad‐spectrum antiseizure medication for the treatment of IGE.

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