Efficacy and tolerability of perampanel in pediatric patients with Dravet syndrome

Yoshitomi, Shinsaku; Takahashi, Yukitoshi; Yamaguchi, Tokito; Imai, Katsumi; Ishii, Atsushi; Hirose, Sachiko; Inoue, Yushi

doi:10.1016/j.eplepsyres.2019.02.014

Cited by 32 publications

(46 citation statements)

References 15 publications

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“…PGTCS-free rates from 0% in Dravet syndrome [ 21 ] and refractory childhood epilepsy [ 40 ] to 88% and 100% in JME [ 16 ]…”

Section: Resultsmentioning

confidence: 99%

“…Outcomes for myoclonic seizures are reported for 24 people with myoclonic seizures associated with IGE in a post-hoc analysis of the RCT [17], in 59 patients treated with perampanel in two nonrandomised interventional studies [11,12] and 151 patients in 14 observational studies (Table 2). These included 66 patients with IGE (mostly JME) [14,16,18], 76 patients with PMEs [11,12,[18][19][20] and three with Dravet syndrome [21].…”

Section: Myoclonic Seizuresmentioning

confidence: 99%

“…13 observational studies N = 3 [38]; N = 8 [21]; N = 8 [15]; N = 4 [40]; N = 115 [14]; N = 18 [45]; N = 17 [18]; N = 6 [35]; N = 9 [39]; N = 4 [46]; N = 4 [16]; in refractory childhood epilepsy [15] to 100% in refractory JME [16] PGTCS-free rates from 0% in Dravet syndrome [21] and refractory childhood epilepsy [40] to 88% and 100% in JME [16] Not extractable in 8 studies No worsening in 2 studies [38,46] Reported in 1/7 and 2/4 children with refractory epilepsy [15,40] ≥ 10% increase from baseline reported in 6/115 patients with IGE (5.2%) at…”

Section: Absence Seizuresmentioning

confidence: 99%

“…The median frequency of absence seizures at baseline was 13.0 in the perampanel group (range 0. [11] and in 70% (7/10) with Lafora disease [12] Reduction in myoclonus severity in PME [11] Subjective myoclonic seizure worsening in at least 1 patient (and ≤ 4) led to discontinuation [11] AE rates 45-80% [11,12] Discontinuation due to AEs in 22% and 30% [11,12] 14 observational studies reported outcomes in patients or subgroups with myoclonic seizures N = 48 IGE [14]; N = 31 [18]; N = 18 [35]; N = 12 PME [19]; N = 11 [45]; 39]; N = 5 JME [16]; N = 3 Dravet [21]; [20]; N = 3 [38]; N = 3 [46]; N = 2 [40]; N = 1 [51] [45]; [46]; N = 4 [15]; N = 4 [40]; N = 3 Dravet [21]; [38]; N = 3 JME [16]; S1, see ESM 4). Results from smaller studies were broadly consistent, with high rates of seizure freedom (Table 4).…”

Section: Absence Seizuresmentioning

confidence: 99%

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Exploring the Evidence for Broad-Spectrum Effectiveness of Perampanel: A Systematic Review of Clinical Data in Generalised Seizures

et al. 2021

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Background The effectiveness of adjunctive perampanel has not been systematically assessed in seizure types other than its approved indications of focal seizures and primary generalised tonic-clonic seizures (PGTCS) in idiopathic generalised epilepsies (IGEs). Objective We aimed to identify and review available evidence on outcomes with perampanel in generalised seizures and epilepsies to examine its potential as a broad-spectrum anti-seizure medication. Methods Bibliographic databases of publications, clinical trials, and conference abstracts were searched up to August 2020 to identify studies reporting seizure or safety outcomes in patients of any age, with any type of epilepsy-associated generalised seizures treated with perampanel. Data extracted from selected records were tabulated by seizure type and syndrome, and analysed qualitatively (PROSPERO protocol CRD42020201564). Results Ninety-one reports met inclusion criteria and were selected: 15 reports of 1 randomised controlled trial (RCT), 8 reports of 4 non-randomised interventional studies, 37 reports of observational studies, 21 case reports and 10 systematic reviews and meta-analyses. Extracted data included 359 patients with PGTCS of any aetiology, 251 with myoclonic seizures, 112 with absence seizures, 50 with tonic seizures and 32 children with epileptic spasms. The most commonly reported epilepsy type was IGE (N = 378) and the most common syndromes were juvenile myoclonic epilepsy (N = 92), progressive myoclonic epilepsies (N = 59) and absence epilepsies (N = 43). The RCT provided Class I evidence of the efficacy and tolerability of adjunctive perampanel for PGTCS in patients aged ≥ 12 years with IGE. Data from other studies provides weaker (observational) evidence of its effectiveness in multiple generalised seizure types, including myoclonic, absence and tonic seizures. There were no patterns suggesting seizure worsening or aggravation in any seizure or epilepsy type. Conclusions The identified studies suggest the potential of perampanel as a broad-spectrum antiseizure medication. Much of the available data, however, come from non-randomised, non-controlled studies and are open to high risk of bias. Further studies are warranted to provide more robust evidence.

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“…PGTCS-free rates from 0% in Dravet syndrome [ 21 ] and refractory childhood epilepsy [ 40 ] to 88% and 100% in JME [ 16 ]…”

Section: Resultsmentioning

confidence: 99%

Section: Myoclonic Seizuresmentioning

confidence: 99%

Section: Absence Seizuresmentioning

confidence: 99%

Section: Absence Seizuresmentioning

confidence: 99%

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Exploring the Evidence for Broad-Spectrum Effectiveness of Perampanel: A Systematic Review of Clinical Data in Generalised Seizures

et al. 2021

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“…Therefore, there is an urgent need to search for a new target for the treatment of Dravet syndrome. Recently, some clinical studies demonstrated that PER treatment reduced seizure frequency and may be effective in patients with Dravet syndrome (Lin et al, 2018;Yoshitomi et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Perampanel Reduces Hyperthermia-Induced Seizures in Dravet Syndrome Mouse Model

Chen

et al. 2021

Front. Pharmacol.

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Treatment options for Dravet syndrome are limited. The aim of this study was to evaluate the antiepileptic effect of the AMPA receptor antagonist perampanel (PER) on a mouse model of Dravet syndrome (Scn1aE1099X/+). We report here that the PER (2 mg/kg) treatment inhibited the spontaneous recurrent seizures and attenuated epileptic activity in Scn1aE1099X/+ mice. In the hyperthermia-induced seizure experiment, PER clearly increased temperature tolerance and significantly ameliorated seizure frequency and discharge duration. PER also demonstrated antiepileptic effects in a cross-over study and a synergistic effect for attenuating heat-induced seizure when given in combination with stiripentol or valproic acid. The results showed that PER effectively decreased the occurrence of spontaneous recurrent seizures and showed significant therapeutic potential for hyperthermia-induced seizures with regard to both susceptibility and severity in a Dravet syndrome mouse model. Potential therapeutic effects of PER for treatment of Dravet syndrome were demonstrated.

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Efficacy of perampanel in pediatric epilepsy with known and presumed genetic etiology

Miao

Zhu²,

Jin

et al. 2023

Ann Clin Transl Neurol

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ObjectiveThe efficacy of perampanel (PER) in pediatric epilepsy with specific etiologies has not been well established. Here, we investigated outcome and predictors of PER treatment in a pediatric cohort with known and presumed genetic etiology.MethodsWe included pediatric patients with potential genetic epilepsy who received PER treatment and underwent whole‐exome sequencing (WES) from January 2020 to September 2021. All patients were followed up for >12 months.ResultsA total of 124 patients were included. Overall response rates were 51.6% and 49.6% at 6 months and 12 months, respectively. Pathogenic or likely pathogenic variants in 27 multiple genes were detected among 58 patients (46.8%) by WES. On performing multivariate logistic regression analysis, only developmental delay (OR = 0.406, P = 0.042) was a negative predictor of treatment response. However, the seizure onset age, positive WES results, and number of ASMs before PER administration were not significantly. Thirteen carriers with variants in the SCN1A gene showed a better response compared to eight patients with other sodium channels (P = 0.007), and to the other 45 patients with positive WES results (OR = 7.124, 95% CI = 1.306–38.860, P = 0.023). Adverse events were only reported in 23 patients, the most common being emotional problems.InterpretationPER is safe and efficacious in pediatric patients with known and presumed genetic etiology. The response rate is comparable to that reported in other pediatric populations, and lower among those with developmental delay. A gene‐specific response to PER is found along with better efficacy links to pathogenic variants in the SCN1A gene.

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Efficacy and tolerability of perampanel in pediatric patients with Dravet syndrome

Cited by 32 publications

References 15 publications

Exploring the Evidence for Broad-Spectrum Effectiveness of Perampanel: A Systematic Review of Clinical Data in Generalised Seizures

Exploring the Evidence for Broad-Spectrum Effectiveness of Perampanel: A Systematic Review of Clinical Data in Generalised Seizures

Perampanel Reduces Hyperthermia-Induced Seizures in Dravet Syndrome Mouse Model

Efficacy of perampanel in pediatric epilepsy with known and presumed genetic etiology

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