Safety and Efficacy of Perampanel as Adjunctive Therapy in Patients with Refractory Focal Epilepsy Over 12 Months: Clinical Experience in a Real-World Setting

Abstract

Background The main purpose of this study is to assess efficacy and tolerability of perampanel (PER), a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonist, as an add-on treatment in adult patients with refractory focal-onset seizures.

Patients and Methods A prospective, open label, observational study was conducted in patients with refractory focal-onset seizures treated with PER at our Epilepsy Unit, from May 2015 to February 2016. Patients were followed up for 1 year. Frequency of seizure and tolerability was assessed every 3 months. Patients were under a polytherapy, and the mean number of concomitant antiepileptic drugs (AEDs) at PER initiation was 2.9.

Results We consecutively enrolled 52 patients (M/F = 18/34). Three were lost on follow-up. Mean age was 38.7 years, with a mean duration of disease of 28.1 years. After 1 year of treatment, 57.14% reported a 50% or greater reduction in seizure frequency; five (10.21%) were seizure free. Six (12.25%) patients reported a reduction lower than 50%. Mean dosage of PER was 7.57 mg. Thirty-one patients were taking enzyme-inducing AEDs (carbamazepine, oxcarbazepine, phenytoin). In this subgroup, the responder rate was 45.2%. Twenty-one patients reported side-effects, most frequently somnolence (11), vertigo/ataxia (6), and aggressiveness (5). Eleven (22.4%) patients reduced or discontinued at least one concomitant AED, while the electroencephalography improved in four (8.16%). Sixteen (32.65%) patients withdrew PER, after a mean duration of 163 days, the mean dosage being 6.4 mg (range 4–12).

Conclusions Adjunctive PER can achieve clinically meaningful improvement, or even seizure freedom, in almost two-thirds of patients suffering from refractory focal-onset epilepsies. It seems similarly safe and well-tolerated. Enzyme-inducing AEDs may limit the efficacy of PER.

Keywords

antiepileptic drugs - efficacy - epilepsy - perampanel - real-world - tolerability

• Reference

• 1 Rektor IPerampanel. a novel, non-competitive, selective AMPA receptor antagonist as adjunctive therapy for treatment-resistant partial-onset seizures.. Expert Opin Pharmacother 2013; 14 (02) 225-235
• 2 Rogawski MA, Hanada T. Preclinical pharmacology of perampanel, a selective non-competitive AMPA receptor antagonist. Acta Neurol Scand Suppl 2013; 197 (197) 19-24
• 3 French JA, Krauss GL, Biton V. et al. Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304. Neurology 2012; 79 (06) 589-596
• 4 French JA, Krauss GL, Steinhoff BJ. et al. Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: results of randomized global phase III study 305. Epilepsia 2013; 54 (01) 117-125
• 5 French JA, Krauss GL, Wechsler RT. et al. Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy A randomized trial. Neurology 2015; 85 (11) 950-957
• 6 Villanueva V, Garcés M, López-González FJ. et al. Safety, efficacy and outcome-related factors of perampanel over 12 months in a real-world setting: The FYDATA study. Epilepsy Res 2016; 126: 201-210
• 7 Gidal BE, Laurenza A, Hussein Z. et al. Perampanel efficacy and tolerability with enzyme-inducing AEDs in patients with epilepsy. Neurology 2015; 84 (19) 1972-1980
• 8 Marson AG, Williamson PR. Interpreting regulatory trials in epilepsy. Curr Opin Neurol 2009; 22 (02) 167-173
• 9 Trinka E, Steinhoff BJ, Nikanorova M, Brodie MJ. Perampanel for focal epilepsy: insights from early clinical experience. Acta Neurol Scand 2016; 133 (03) 160-172
• 10 Steinhoff BJ, Bacher M, Bast T. et al. First clinical experiences with perampanel-the Kork experience in 74 patients. Epilepsia 2014a 55 (Suppl. 01) 16-18
• 11 Steinhoff BJ, Hamer H, Trinka E. et al. A multicenter survey of clinical experiences with perampanel in real life in Germany and Austria. Epilepsy Res 2014b 108 (05) 986-988
• 12 Coyle H, Clough P, Cooper P, Mohanraj R. Clinical experience with perampanel: focus on psychiatric adverse effects. Epilepsy Behav 2014; 41: 193-196
• 13 Gidal BE, Ferry J, Majid O, Hussein Z. Concentration-effect relationships with perampanel in patients with pharmacoresistant partial-onset seizures. Epilepsia 2013; 54 (08) 1490-1497
• 14 Maurousset A, Limousin N, Praline J, Biberon J, Corcia P, De Toffol B. Adjunctive perampanel in refractory epilepsy: experience at tertiary epilepsy care center in tours. Epilepsy Behav 2016; 61: 237-241
• 15 De Liso P, Vigevano F, Specchio N. et al. Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies-an Italian observational multicenter study. Epilepsy Res 2016; 127: 93-100
• 16 Krauss GL, Serratosa JM, Villanueva V. et al. Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures. Neurology 2012; 78 (18) 1408-1415
• 17 Rektor I, Krauss GL, Bar M. et al. Perampanel Study 207: long-term open-label evaluation in patients with epilepsy. Acta Neurol Scand 2012; 126 (04) 263-269
• 18 Krauss GL, Perucca E, Kwan P. et al. Final safety, tolerability, and seizure outcomes in patients with focal epilepsy treated with adjunctive perampanel for up to 4 years in an open-label extension of phase III randomized trials: Study 307. Epilepsia 2018; 59 (04) 866-876
• 19 Juhl S, Rubboli G. Perampanel as add-on treatment in refractory focal epilepsy. The Dianalund experience. Acta Neurol Scand 2016; 134 (05) 374-377
• 20 Steinhoff BJ, Ben-Menachem E, Ryvlin P. et al. Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: a pooled analysis of three phase III studies. Epilepsia 2013; 54 (08) 1481-1489
• 21 Shah E, Reuber M, Goulding P, Flynn C, Delanty N, Kemp S. Clinical experience with adjunctive perampanel in adult patients with uncontrolled epilepsy: a UK and Ireland multicentre study. Seizure 2016; 34: 1-5
• 22 Singh K, Shah YD, Luciano D, Friedman D, Devinsky O, Kothare SV. Safety and efficacy of perampanel in children and adults with various epilepsy syndromes: a single-center postmarketing study. Epilepsy Behav 2016; 61: 41-45