The Efficacy And Safety Analysis Of Perampanel For The Treatment Of Epilepsy In Children

BackgroundEpilepsy is one of the common chronic neurological diseases with the highest incidence in childhood,which has adverse effects on children’s cognition,physical and mental health,social function and so on.It also increases family economic and psychological pressure,and at the same time exists social discrimination and violation of human rights.Most of the patients achieved seizure freedom with approximately medical treatment,but about 1/3 of patients can not be completely controlled and develop into drug-resistant epilepsy.Control seizures play an important role in improving quality of life.At pre sent,anti-seizure medications is given priority.With the clinical development and application of anti-seizure medications,the third generation of new anti-seizure medications are available,including perampanel(PER).PER is a selective non-co mpetitive α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid(AMPA)recep tor antagonist and exerts anti-epileptic effect by inhibiting excitatory transmissi on caused by glutamate.Since it was listed in China in 2019,the indications of PER have gradually expanded.At present,it has been approved for single drug and additive treatment of patients with partial seizures(with or without secondary generalized seizures)aged above 4 years old in China.At present,the application of PER is not wildly used in children epilepsy,and evaluation on its efficacy and safety is still not adequate.Therefore,this study evaluates the efficacy and safety of PER in epilepsy in children by retrospective analysis and comparison of seizures before and after the addition of PER,in order to provide clinical experience for the application of PER in children.Objective1.To retrospectively observe the clinical efficacy of perampanel in epilepsy in children.2.To evaluate the safety of perampanel by recording its adverse in epilepsy in children.Methods1.The clinical data of 29 children with epilepsy treated with PER in pediatrics of the First Affiliated Hospital of Zhengzhou University from August 2020 to November 2021 were collected retrospectively.The base line of seizures and 1,3,6 months after the application of PER were compared,and the related adverse were collected to evaluate the efficacy and safety of PER.The patients were excluded for less than 3 months.2.Adopt spss21.0 for statistical analysis,the measurement data conforming to normal distribution are expressed in(x±s),the measurement data of non normal distribution are expressed in median and quartile[M(P25,P75)],the counting data are expressed in frequency and percentage,the t-test is used for inter group comparison,and the Fisher exact probability method is used for inter group comparison of binary data,Rank sum test was used for the comparison between non normal distribution and multi-classification ordered data groups;P<0.05 was statistically significant.Results1.General information:A total of 29 children with epilepsy were included in this study,male:female=1.1:1(15/14 cases),average age(10.79± 2.92)years,average age at onset(5.43± 3.02)years old.The median disease duration before PER was 5 years,and the median follow-up time was 8 months.The average age at the time of PER application was(10.24±2.75)years,of which 19 cases(63.3%)were 4-12 years old,and 10 cases(36.7%)were≥12 years old.Before the application of PER,the attack frequency was between more than 20 times/d to 1 time/month.In terms of seizure type,22 cases(75.9%)had focal seizures,of which 2 cases(6.9%)were focal seizures without consciousness,and 20 cases(69%)were focal seizures with consciousness.6 cases(20.7%)were generalized seizures,which were generalized tonic-clonic seizure.1 case(3.4%)was unknown onset seizure.Epilepsy syndrome was identified in 4 cases(13.8%),all of which were BECTS.There were 9 cases(31.0%)with clear etiology,of which 7 cases(24.1%)were structural etiology,including microgyria(1 case),hippocampal sclerosis(1 case),focal cortical dysplasia(3 cases),and encephalomalacia(1 case),glial encephalopathy(1 case);immune etiology 1 case(3.5%),which was secondary epilepsy to auto-immune encephalitis;infectious etiology 1 case(3.5%).Before the application of PER,the numbers of ASMs used were between 0 and 4,the median type of ASMs was 2.6 cases(20.7%)used 1 type of ASMs,6 cases(20.7%)used 2 types of ASMs,and 10 cases(34.5%)used 3 types of ASMs,3 cases(10.3%)used 4 ASMs,and 4(13.8%)with PER monotherapy.2.Efficacy:The frequency of seizures at 1,3,and 6 months of PER application was statistically significant compared to baseline seizure frequency(baseline vs 1 month:P=0.035;baseline vs 3 months:P=0.006;baseline vs 6 months:P=0.027).At 1,3,and 6 months of PER application,17(17/29,58.6%),18(18/29,62.1%),and 8(8/19,42.1%)children had a baseline level decreased by≥50%,and 11 cases(11/29,37.9%),13 cases(13/29,44.8%),and 7 cases(7/19,36.8%)had no seizures,respectively.There was no significant difference in the effective rate and seizure-free rate at 1,3 and 6 months(P=0.368,P=0.815).At the last follow-up,16 patients(55.2%)had seizure frequency decreased by≥50%compared with the baseline level,14 patients(48.3%)had no seizures,and 13 patients(44.8%)were ineffective.Three of the 4 children with PER monotherapy and three of the 4 children with BECTS were seizure-free,and 1 was ineffective respectively.Comparing those who were effective(16/29,55.2%)and those who were ineffective(13/29,44.8%)with PER treatment,it was found that the effective group had fewer numbers of ASMs combined before PER(P=0.004),and there was no statistical significance in age of onset,gender,course of disease,age of adding PER,maintenance dose of PER,type of attack,frequency of attack,etiology and whether enzyme-inducer anti-epileptic drugs were used.3.Retention rate and safety:At the last follow-up,the overall retention rate of PER was 86.2%(25/29),and 4 patients discontinued the drug after half a year due to prolonged seizure time(2 cases)and no improvement in seizures(2 cases).9 patients(31.0%)experienced at least one adverse reaction,mainly somnolence and fatigue(5 cases),irritability(4 cases),in addition to ataxia(1 case),dizziness(1 case),the degree is mild,and the adverse reactions are gradually alleviated with the prolongation of the medication time.Among the 4 children treated with monotherapy,1 had adverse reactions,manifested as irritability,3 remained at the last follow-up,and 1 discontinued the medication after 3 months because the seizures did not improve.The retention rate and safety were not statistically significant in different age groups(4-12 years old and≥12 years old)(P=0.590,P=1.000).Conclusions1.Perampanel monotherapy or add-on therapy can effectively reduce the frequency of epileptic seizures in children,and it is effective for different age groups and seizure types.2.Perampanel has good safety and tolerability as a single drug or as an additive in the treatment of epilepsy in children.The main manifestations are drowsiness,fatigue,and irritability,the degree of which is mild,and can be gradually alleviated or disappeared with the prolongation of medication time.