A Meta-Analysis Of Perampanel In The Adjunctive Treatment Of Intractable Partial-Onset Epilepsy

Objectivesperampanel,whose trade name is Fycompa,was researched and developed by Eisai Co.Ltd in Japan.Perampanel is the only orally active noncompetitive and highly selective antagonist at the AMPA receptor nowadays.Perampanel is not only a third-generation antiepileptic drug which isused in refractory partial-onset epilepsy but also the one and only AEDs which inhibits the AMPA receptor.Nowadays Published randomised controlled trials(RCTs)had small sample sizes,and meta-analyses had included too few studies to get appropriate results for the tolerability,efficacy and safety of perampanel.So we conduct this meta-analysis with a larger dataset and suitable design.The purpose for conducting this Meta-analysis is to appraise the efficacy and safety of perampanel in the treatment of refractory partial-onset epilepsy.Methodsthe RCTs of perampanel in treatment of refractory partial-onset seizures were systematically searched from CNKI,VIP,PubMed,EMbase,Cochrane Library online.The research language is limited to English and Chinese,and the research object is limited to human.The type of the literature was randomized controlled trial.The data of perampanel were collected from the establishment of the database to January 2019and all of the outcomes were analyzed by meta-analysis with Stata 15.0 software.We used the combination of subject and free terms to conduct the keyword retrieval.Cochrane's high accuracy and sensitivity of the retrieval strategy of randomized controlled trials(RCTs)was involved.The literature retrieved were imported into medical V5 software to remove duplication,after the reviewing by two independent researchers respectively and rule out the ones that were not related to this study obviously.Then read through the text carefully and find out the relevant literatures according to fixed inclusion and exclusion criteria.Likewise,the basic characteristics of the study and subjects,research evaluation outcomes,preliminary results of these literatures were collected.All of the process must be performed independently by the two researchers.If the two researchers disagree with each other,they may ask for a third one or mutual consultation for the determination of the consensus.The final selected randomized controlled trials of the treatment of refractory partial-onset seizures with perampanel was meta-analyzed using the Stata15.0 software and Review Manager 5.3.We chose the relative risk(RR)and 95%confidence interval on behalf of the estimated effect size,and the heterogeneity was evaluated by Q test and I~2 value.The publication bias was determined by funnel plot,and the sensitivity of the results was analyzed by deletion method to evaluate the reliability of the results.ResultsA total number of 265 de-duplicated literatures were retrieved,and five English lite ratures,involving six RCTs,were finally obtained after screening according to the inc-lusion and exclusion criteria of literatures,with 2388 patients who suffered from refractory partial-onset seizures,1707 in perampanel group and 801 in placebo group.Meta-analysis results showed that there was a significant difference between perampanel 4mg[RR=4.15,95%CI(1.18,14.63)]?8mg[RR=3.53,95%CI(1.35,9.27)]?12mg[RR=4.58,95%CI(.44,14.63)],and placebo in term of seizure-free rate,and percentage of patients achieving 50%reduction in seizure frequency also has sign ificant difference between perampanel 4mg[RR=1.39,95%CI(1.08,1.79)]?8mg[RR=1.81,95%CI(1.49,2.19)]?12mg[RR=1.90,95%CI(1.42,2.563)].The occurance of severe adverse reaction of perampanel groups of 4mg,8 mg,12 mg had no statistic differernce with placebo(P<0.05).Incidence of withdrawal of 8mg and 12mg was significantly higher than placebo(P<0.05),however the same in perampanel 4mg has no statistical difference with placebo.ConclusionCompared with the placebo,there was significant effectiveness in the efficacy assessment of perampanel,and the safety was significant marked in the meantime.The major side effects include somnolence and headache,while in an acceptable range.From the above,when perampanel is added as a drug for the treatment of intractable partial-onset epilepsy for clinical use.,the frequency of seizures can be effectively reduced,and even no seizures can be achieved clinically.