Perampanel in 12 patients with Unverricht‐Lundborg disease

Crespel, Arielle; Gélisse, Philippe; Tang, Ngoc Phuong Loc; Genton, Pierre

doi:10.1111/epi.13662

Cited by 64 publications

(57 citation statements)

References 13 publications

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“…When perampanel was given as add‐on therapy for 12 patients with Unverricht‐Lundborg disease, 10 experienced a clear clinical response of myoclonus, some at a dose as low as 2 mg, and 5 were able to reduce their concomitant medication . Epileptic seizures stopped in all 6 patients who experienced generalized tonic–clonic or myoclonic seizures (100%).…”

Section: Perampanel In Clinical Practicementioning

confidence: 99%

Perampanel: Does it have broad‐spectrum potential?

Potschka

Trinka

2018

Epilepsia

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This article reviews the profile of perampanel, a novel noncompetitive α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor antagonist, and its role as a potential broad-spectrum antiepileptic drug in the treatment of epilepsy. For this narrative review, data were collected using specified search criteria. Articles reporting the evidence for perampanel's efficacy from preclinical models, phase 3 clinical studies, observational studies, and descriptive evidence were included. AMPA receptors play a key role in mediating the action of glutamate at the excitatory synapse. Preclinical research showed the AMPA receptor blockade to constitute a promising target for antiepileptic drug therapy. In animal models, perampanel proved to be protective against seizures and reduce seizure severity and duration. Four phase-3 randomized controlled trials (3 in patients with focal seizures and one in primary generalized tonic-clonic seizures in idiopathic generalized epilepsy) have been completed. In focal (partial) onset seizures, perampanel (4, 8, and 12 mg) significantly reduced seizure frequency per 28 days (23.3%-28.8% vs 12.8%; P < .01) and responder rates (≥50% reduction in seizures) (28.5%-35.3% vs 19.3%; P < .05) compared with placebo. In primary generalized tonic-clonic seizures, perampanel 8 mg resulted in greater reduction in seizure frequency per 28 days (-76.5% vs -38.4%; P < .0001) and responder rate (64.2% vs 39.5%; P = .0019) than placebo. The efficacy, safety, and tolerability of perampanel have been reproduced in real-world clinical practice, and the agent has been shown to be effective in other epilepsy syndromes. Perampanel is a potentially broad-spectrum antiepileptic drug with a novel mechanism of action that may be a useful addition for patients with epilepsy with various seizure types. The availability of novel antiepileptic drugs for epilepsy treatment enables more individualized treatment for these patients.

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Section: Perampanel In Clinical Practicementioning

confidence: 99%

Perampanel: Does it have broad‐spectrum potential?

Potschka

Trinka

2018

Epilepsia

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“…Published real‐world data with perampanel is mainly from patients with focal seizures, or small case series in specific seizure types, like progressive myoclonic epilepsies or drug‐resistant myoclonic seizures . The phase III perampanel trial in IGE included few patients with myoclonic or absence seizures, so the effect of perampanel on these seizure types could not be determined .…”

Section: Introductionmentioning

confidence: 99%

Perampanel in routine clinical use in idiopathic generalized epilepsy: The 12‐month GENERAL study

et al. 2018

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Summary Objective To analyze the effectiveness and tolerability of perampanel across different seizure types in routine clinical care of patients with idiopathic generalized epilepsy (IGE). Methods This multicenter, retrospective, 1‐year observational study collected data from patient records at 21 specialist epilepsy units in Spain. All patients who were aged ≥12 years, prescribed perampanel before December 2016, and had a confirmed diagnosis of IGE were included. Results The population comprised 149 patients with IGE (60 with juvenile myoclonic epilepsy, 51 generalized tonic–clonic seizures [GTCS] only, 21 juvenile absence epilepsy, 10 childhood absence epilepsy, 6 adulthood absence epilepsy, and one Jeavons syndrome). Mean age was 36 years. The retention rate at 12 months was 83% (124/149), and 4 mg was the most common dose. At 12 months, the seizure‐free rate was 59% for all seizures (88/149); 63% for GTCS (72/115), 65% for myoclonic seizures (31/48), and 51% for absence seizures (24/47). Seizure frequency was reduced significantly at 12 months relative to baseline for GTCS (78%), myoclonic (65%), and absence seizures (48%). Increase from baseline seizure frequency was seen in 5.2% of patients with GTCS seizures, 6.3% with myoclonic, and 4.3% with absence seizures. Perampanel was effective regardless of epilepsy syndrome, concomitant antiepileptic drugs (AEDs), and prior AEDs, but retention and seizure freedom were significantly higher when used as early add‐on (after ≤2 prior AEDs) than late (≥3 prior AEDs). Adverse events were reported in 50% of patients over 12 months, mostly mild or moderate, and irritability (23%), somnolence (15%), and dizziness (14%) were most frequent. Significance In routine clinical care of patients with IGE, perampanel improved seizure outcomes for GTCS, myoclonic seizures, and absence seizures, with few discontinuations due to adverse events. This is the first real‐world evidence with perampanel across different seizure types in IGE.

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“…6 In this latter study, the population included 65 patients who had myoclonic seizures due to IGE. 13 Based on this preliminary experience, and because of the limited options, some Spanish epileptologists have started to prescribe perampanel for patients with drug-resistant myoclonic seizures. 6,7 Recently, two case reports 8,9 and a case series 10 have described positive results with adjunctive perampanel in Lafora disease, two positive case reports in post-anoxic myoclonic status epilepticus, 11,12 and a case series of 12 patients with Unverricht-Lundborg disease.…”

Section: Introductionmentioning

confidence: 99%