Observation Of Clinical Effects And Factors Analysis Of Adjunctive Perampanel For Patients With Drug-resistant Epilepsy

Background20% to 30% of total epilepsy was found to be drug-resistant,which causing a huge disease burden on individuals,families,and society.As an important part of drugresistant epilepsy,developmental and epileptic encephalopathies(DEE)is a new concept first proposed by the International League Against Epilepsy(ILAE)in its 2017 position paper on the new classification of seizures and epilepsy,which are characterized by refractory seizures starting in infancy or childhood and developmental delay or regression.As an important component of drug-resistant epilepsy(DRE),epilepsy in DEE is always intractable.Perampanel(PER)is a novel non-competitive α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate(AMPA)receptor antagonist.Adjunctive PER for partial-onset seizures(with or without secondary generalization)effectively reduced seizure frequency and possessed a favorable tolerability profile since its offering.However,the effectiveness and safety of DRE especially DEE still need more evidence.Objective1.To study the clinical efficacy,safety,and tolerability of Perampanel adjunctive for DRE.2.Analyze the relevant factors that affect efficacy,safety,and tolerability of PER.3.Provide a basis for DRE,especially DEE patients on personalized medication selection.Method1.This study included 70 DER treated with PER supplementation at the Epilepsy Center of the Second Affiliated Hospital of Guangzhou Medical University from January 1,2021 to December 31,2022.According to the diagnostic criteria for DEE,70 patients were divided into a DEE group and a non-DEE group.Record the basic information of all patients,including gender,age,age of onset,past history,seizure,epilepsy or epilepsy syndrome,baseline number and type of combined anti-seizure medications(ASMs),genetic data(genetic variation results),EEG,and imaging data.2.Two groups of patients were followed up at 1 month,3 months,and 6 months after the addition of PER.The frequency and form of seizures,drug related adverse events(AEs),the retention ratio of PER,and the reason for discontinuation were recorded.3.Explore the reduction in seizure frequency,the response rate of PER,the incidence of AEs,and the retention ratio of PER of patients in two groups at different follow-up stages.4.Patients who completed a 6-month follow-up were divided into a PER response group and a non-response group based on clinical efficacy.Statistical differences were analyzed between the two groups in terms of gender,seizure type,brain magnetic resonance imaging,epilepsy syndrome type,and pathogenic gene type.Relevant factors affecting efficacy,safety,and tolerance were explored.Result1.A total of 70 DRE treated with PER were included in this study,with 45 males(64.3%)and 25 females(35.7%),including 44 in the DEE group and 26 in the nonDEE group.There were statistical differences between the two groups in terms of age,age of onset,seizure type,and type of pathogenic gene variation(P<0.001).There was no significant difference in sex,family history,brain MRI and number of baseline combined ASMs between two groups(P>0.05).2.The median of seizure frequency(quartile interval)of all patients was5.5(28.00)times a month before using PER and 2.58(13.58)times a month after adding PER.The median of seizure frequency(quartile interval)in the DEE group decreased from 4.0(26.13)to 2.83(17.24)times per month,while that in the non-DEE group decreased from 8.0(28.00)to 2.00(6.00)times per month.There was a statistically significant difference in seizure frequency between the two groups before and after the addition of PER(P<0.05).During the 1-month,3-month,and 6-month follow-up,the response rates of PER in all patients were 52.9%、53.6%、58.8%,which in DEE group were 50.0%,52.3%,and 61.4%,respectively,while in the non DEE group were 42.3%,56.0%,and 54.2%,respectively.3.Within 6 months of follow-up,23 patients(32.8%)experienced AEs,with 14 cases in the DEE group and 9 cases in the non-DEE group.Among them,3 cases(4.0%)discontinuation due to adverse reactions.Among all AEs,irritability was the most common(10 cases,14.3%),followed by dizziness(5 cases,7.1%),somnolence(4 cases,5.7%),and delayed response(3 cases,4.3%).Other AEs also included falls,hyperactivity,attention deficit,nausea,sleep disorders,and aggressive behavior.4.Follow-up at 1-month,3-month,and 6-month,the PER retention rates were100%,89.9%,and 80.9%,respectively,The retention rates in the DEE group and nonDEE group at month 3 were 84.1% and 92.0%,respectively.And the rates at month 6were 79.5% and 83.3%,respectively.There was no statistically significant difference in the retention rates between the two groups(P>0.05).5.The differences in patient gender,seizure and epilepsy syndrome have no significant impact on the efficacy of PER.The response rate of patients which with abnormal results in head magnetic resonance is lower than those without abnormalities.78.3% patients with voltage-gated ion channels disease show great effect after using PER.PER combined with enzyme inducer antiepileptic drugs for drug-resistant epilepsy not increased the incidence of AEs.Conclusions1.The overall response rate of PER treatment for DRE patients is 58.6%,and there is no difference between the DEE group and non-DEE group.2.The common adverse events are irritability,dizziness,somnolence,delayed response,and attention deficit.All adverse reactions are mild to moderate,and most can be alleviated by slowing down the titration speed or reducing the drug dose.3.Adjunctive PER for patients with mutations in ion channel genes show great effect.4.The retention rate of PER for DRE at month 6 was 80.9%,and the reasons for discontinuation were mostly due to adverse reactions or poor efficacy.