Perampanel as precision therapy in rare genetic epilepsies

Nissenkorn, Andreea; Kluger, Gerhard; Schubert‐Bast, Susanne; Bayat, Allan; Bobylova, Marya; Bonanni, Paolo; Ceulemans, Berten; Coppola, Antonietta; Bonaventura, Carlo Di; Feucht, Martha; Fuchs, Anne; Gröppel, Gudrun; Heimer, Gali; Herdt, Brigitte; Куликова, С.Л.; Мukhin, K. Yu.; Nicassio, Stefania; Orsini, Alessandro; Panagiotou, Maria; Pringsheim, Milka; Puest, Burkhard; Пылаева, О. А.; Ramantani, Georgia; Τσεκούρα, Μαρία; Ricciardelli, Paola; Sagie, T.; Stark, B.; Striano, Pasquale; Baalen, Andreas van; Wachter, Matthias De; Irelli, Emanuele Cerulli; Cuccurullo, Claudia; Stülpnagel, Celina von; Russo, Angelo

doi:10.1111/epi.17530

Cited by 21 publications

(12 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous case series studies displayed a similar response rate. 10,13,21,22 A recent study in epilepsy associated with a SCN1A pathogenetic variant (responder rate: 11 of 17, 64.7%) was in line with our findings. 22 We then reviewed the published variants in SCN1A gene with PER treatment, but no discrepant distribution of effective and ineffective variants were found (sup Fig.…”

Section: Discussionsupporting

confidence: 92%

“…In our cohort 11 out of 13, SCN1A ‐related patients were diagnosed with Dravet syndrome, and 63.6% (7/11) of them responded to PER treatment. Previous case series studies displayed a similar response rate 10,13,21,22 . A recent study in epilepsy associated with a SCN1A pathogenetic variant (responder rate: 11 of 17, 64.7%) was in line with our findings 22 .…”

Section: Discussionsupporting

confidence: 92%

“…PER partially suppressed seizures and involuntary movements in two patients with early‐onset epileptic encephalopathy caused by the GNAO1 gene, reached a 100% seizure reduction. Interestingly, Nissenkorn et al 22 reported the same finding (responder rate: 4 of 4, 100%) for those with pathogenic variants in the GNAO1 gene. Including ours, there have been six reported cases.…”

Section: Discussionmentioning

confidence: 68%

See 2 more Smart Citations

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

Miao

Zhu²,

Jin

et al. 2023

Ann Clin Transl Neurol

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 68%

See 1 more Smart Citation

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

Miao

Zhu²,

Jin

et al. 2023

Ann Clin Transl Neurol

View full text Add to dashboard Cite

show abstract

“…These findings were similar to the previous study conducted on a similar population of childhood epilepsy in China 21 . PER was also found to be effective in different epilepsy subtypes (Table 1), as previously described in the literature 1,22,23 . PER efficacy seemed higher in focal onset epilepsy subtypes, although no statistically significant results were found.…”

Section: Discussionsupporting

confidence: 92%

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

View full text Add to dashboard Cite

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.

show abstract

“…Furthermore, PER showed efficacy and appropriate tolerability among other epilepsy syndromes that are known to be refractory to many ASMs including Lennox-Gastaut syndrome ( 20 ), nonetheless, firm conclusions are still not established on its use as a first-line treatment and more studies are needed to assess its long-term effects. It also presented potential in treating patients with refractory seizures compared to other ASMs ( 16 ), however, several possible adverse events for its administration have been reported such as dizziness, somnolence, headache, and fatigue which was frequently reported ( 21 - 23 ) as well as other psychiatric side effects ( 17 , 19 , 24 ). Moreover, only a few studies investigated and assessed the use of PER in patients with DS ( 24 - 30 ).…”

Section: Introductionmentioning

confidence: 99%

Efficacy and tolerability of perampanel in pediatric patients with Dravet syndrome

Muthaffar,

Bamaga,

Alyazidi

et al. 2024

Transl Pediatr

View full text Add to dashboard Cite

Background In 1978, Charlotte Dravet first described a form of epilepsy termed Dravet syndrome (DS). It is a form of genetic epilepsy with early-onset, intractable epilepsy episodes, and neurodevelopmental delay. In children, DS can lead to refractory seizures that are resistant to standard therapy. Recently, perampanel (PER) was approved as an antiepileptic drug for patients as young as 4 years old. Methods The medical records were retrospectively reviewed and patients with DS who used PER were included in this study. The diagnosis was established using whole-exome sequencing, and the collected data included the patients’ demographic characteristics, seizure pattern, PER dosage, laboratory and imaging findings. Results This study included 18 pediatric patients with a clinical diagnosis of DS. The mean age of PER initiation was 7.67±3.865. Most patients had two types of seizures (61.1%) followed by three types (22.2%), with generalized tonic-clonic being the most frequently reported type of seizure. The mean efficacy of PER was 29.17%±29.368%, and only one patient had an efficacy of 100%. Moreover, patients aged 8 years and younger presented with higher efficacy than those who were older (49.17%±34.120% vs. 19.17%±21.829%, P=0.03). Conclusions This study presented supporting evidence of the promising therapeutic effect of PER among patients with DS. PER can be considered one of the treatment options for this group of patients. However, several patients presented with unfavorable side effects that led to medication cessation. Future multicenter studies are required to explore further treatment options for patients with DS.

show abstract

Perampanel as precision therapy in rare genetic epilepsies

Cited by 21 publications

References 20 publications

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

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

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

Efficacy and tolerability of perampanel in pediatric patients with Dravet syndrome

Contact Info

Product

Resources

About