A Meta-analysis Of The Efficacy And Safety Of Interleukin-17A Inhibitors In The Treatment Of Psoriatic Arthritis

Objective: Interleukin 17A(IL-17A)inhibitor is a novel drug for the treatment of Psoriatic arthritis(Ps A),but the evidence for its efficacy and safety is insufficient.This study evaluated the efficacy and safety of IL-17 A inhibitors in the treatment of Ps A by analyzing the updated data of relevant randomized controlled trials(RCTs),and then ranked the probability of the differences in efficacy and safety of IL-17 A inhibitors,so as to provide evidence-based medicine reference for clinicians.Methods: Literatures related to IL-17 A inhibitors in the treatment of Ps A were searched on CNKI,Wanfang,VIP,Ovid,MEDLINE,EMbase,Pubmed,The Cochrane Central Register of Controlled Trials database.Literature was screened according to pre-established inclusion and exclusion criteria to obtain relevant RCTs.The search date is from the database construction to April 2022,and the language limit is Chinese and English.For the included data,Review Manager 5.3 statistical software was first used for quality evaluation and metaanalysis of the included studies to evaluate the efficacy and safety of IL-17 A inhibitors in Ps A treatment.Then,frequency-based Stata16.0 software was used for network metaanalysis to evaluate the differences in efficacy and safety of IL-17 A inhibitors.The primary outcome measure of efficacy was 20% response(ACR20)as determined by the American college of rheumatology(ACR)criteria.Secondary outcome measures were ACR50/70,psoriasis area severity index(PASI)75% remission(PASI75),PASI90/100,the number of patients recovering from dactylitis and enthesitis,minimal disease activity(MDA),health assessment questionnaire-disability index minimally clinically important difference(HAQDI MCID).Safety measures included total adverse events and serious adverse events.Results: After searching the database,a total of 2130 literatures were obtained,and 13 literatures were finally included,including 14 RCTs,including 5115 adult patients with Ps A.(1)Results of effectiveness evaluation:1)Meta analysis:Patients treated with an IL-17 A inhibitors compared with placebo,ACR20[14 RCTs,OR=3.82,95%CI(3.32,4.39),P<0.00001];ACR50[14 RCTs,OR=5.30,95%CI(4.34,6.47),P<0.00001];ACR70[13 RCTs,OR=6.53,95%CI(4.72,9.04),P<0.00001];PASI75[12 RCTs,OR=12.04,95%CI(9.84,15.64),P<0.00001];PASI90[11 RCTs,OR=10.38,95%CI(7.86,13.70),P<0.00001];PASI100[7 RCTs,OR=12.71,95%CI(7.62,21.19),P<0.00001];Dactylitis resolution[7 RCTs,OR=3.32,95%CI(2.60,4.23),P<0.00001];Enthesitis resolution[7 RCTs,OR=2.69,95%CI(1.96,3.68),P<0.00001];MDA[4 RCTs,OR=4.77,95%CI(3.38,6.72),P<0.00001] and HAQ-DI MCID[4 RCTs,OR=2.91,95%CI(2.26,3.74),P<0.00001].Where OR refers to odds ratio,95%CI refers to 95% confidence interval,and P refers to probability value of statistic.Since the OR values are all greater than 1,and95%CI values do not include 1,P<0.05,therefore,IL-17 A inhibitors significantly alleviated various pathological degrees of Ps A patients.2)Rank the probability of results of network meta-analysis(from highest to lowest efficacy):(1)ACR20: Bimekizumab(97.4%,the probability of becoming the best drug was97.4%)> Secukinumab(60.4%)> Ixekizumab(56.6%)> Brodalumab(35.6%)> Placebo(0%).(2)ACR50: Bimekizumab(78.6%)> Ixekizumab(67.3%)> Secukinumab(61.9%)>Brodalumab(42.2%)> Placebo(0%).(3)ACR70: Ixekizumab(81.9%)> Secukinumab(69.7%)> Bimekizumab(59.4%)>Brodalumab(38.8%)> Placebo(0.2%).In addition,bimekizumab,brodalumab and ixekizumab ranked first in the probability of PASI75/90/100,respectively.Secukinumab ranked first in probability of recovery from dactylitis and enthesitis.In terms of MDA and HAQ-DI MCID,ixekizumab ranked first.Meta-analysis and network meta-analysis showed that IL-17 A inhibitors had significantly higher efficacy than placebo in ACR20/50/70,PASI75/90/100,recovery of dactylitis and enthesitis,MDA and HAQ-DI MCID,and the differences were statistically significant.Considering the efficacy of the primary outcome indicators and secondary outcome indicators,this study recommended bimekizumab as the most effective drug for Ps A treatment.Ixekizumab is recommended as the first choice in this study for patients with severe joint disease seeking maximum remission,but the number of beneficiaries is small.(2)Results of safety evaluation:Meta analysis:Compared with placebo,total adverse events with IL-17 A inhibitors [13 RCTs,OR=1.17,95%CI(0.98,1.38),P=0.08];Serious adverse events [13 RCTs,OR=1.00,95%CI(0.72,1.39),P=1.00].Since all 95%CI values contained 1,IL-17 A inhibitors did not increase total adverse events and serious adverse events,and the difference was not statistically significant.Since there was no statistically significant difference in safety between the two groups,no network meta-analysis was performed.Conclusion: IL-17 A inhibitors can significantly relieve bone and joint(including arthritis,dactylitis and enthesitis)and skin lesions in Ps A patients,without increasing total adverse events and serious adverse events,however,attention should be paid to the possible risk of total adverse events in the course of medication.Considering comprehensive efficacy and safety,when the patient’s condition is mild,bimekizumab is recommended as the most effective drug for Ps A treatment in this study according to the efficacy ranking of primary and secondary outcome indicators.Ixekizumab is recommended as the first choice in this study for patients with severe joint disease seeking maximum remission,but the number of beneficiaries is small.Therefore,individualized selection should be made according to different needs and states of patients.