The Efficacy And Safety Of Anti-Interleukin-17 Antibody For The Treatment Of Psoriasis:a Network Meta-Analysis

BackgroundPsoriasis(PsO)is a common inflammatory skin disease.Its characteristic skin lesions are papules and plaques overlying silvery white scales,which are confined to one place or widely distributed throughout the skin.It has a long disease course and is easy to relapse.Compared with traditional drugs,the emergence of biologics has opened up a new situation in the treatment of psoriasis,especially in 2019,anti-interleukin-17(IL-17)antibodies,new bio-targeted drugs,is applied for the clinical treatment of psoriasis in China,provide a new option for the treatment of psoriasis.The rapid development of this kind of biological agent has led to an urgent need to understand its efficacy and safety.ObjectivesUsing network meta-analysis(NMA)to make direct or indirect comparisons to evaluate the efficacy and safety of anti-IL-17 antibodies in the treatment of psoriasis and rank them,for providing certain clinical reference in the selection of biological agents in psoriasis.Data and methodsA comprehensive literature search was performed in the databases of PubMed,Embase,Cochrane Library,CNKI,Wanfang,and VIP.The retrieved time ranged from January 1st,2000 to December 29th,2020,with the languages confined to Chinese and English.The literatures were screening according to the pre-set inclusion and exclusion criteria.RevMan5.3 software was adopted to extract and synthesize the related data of the randomized controlled trial(RCT)about anti-IL-17 antibodies(Secukinumab,Ixekizumab,and Brodalumab)treated psoriasis.The quality of the included studies was evaluated by 2 researchers according to the Cochrane Systematic Review Manual Version 5.3.0.PASI75(the psoriasis area and severity index decreased by 75%from the baseline)and PASI100 were used as the outcome indicators for evaluating the efficacy,and the incidence of adverse reactions(AE)and serious adverse reactions(SAE)were used as the outcome indicators for evaluating the safety.The publication bias and the inconsistency between direct and indirect evidence were evaluated using comparing-correcting funnel diagram,node analysis and loop inconsistency analysis.This article only analyzed the literatures that selected patients with plaque psoriasis who needed systematic treatment as the research object,considering the following situations:the plaque type is the most common type of psoriasis;there were few randomized controlled studies about anti-IL-17 antibody treated other types of psoriasis;the network meta-analysis need being based on the relevant data of many completed randomized controlled studies.Although some patients with a long medical history may have joint symptoms,this study does not analyze the outcome indicators of joints for the time being.ResultsA total of 18 articles(21 studies)were included,and a total of 14863 patients with plaque psoriasis were included.Four studies were classified as "high bias risk"and the remaining as "uncertain bias risk".According to the included literature,secukinumab is divided into low-dose group(150mg)and high-dose group(300mg),ixekizumab is divided into 80mg once every 4 weeks(Q4W)low-frequency group and 80mg once every 2 weeks(Q2W)high-frequency group,brodalumab is divided into a low-dose group(140mg)and a high-dose group(210mg).Among them,there were three positive control drugs(having direct comparison with one or more of the three anti-IL-17 antibodies):etanercept,ustekinumab and guselkumab.Including placebo,a total of 10 treatment measures were contained(anti-IL-17 antibody intervention group and control group are collectively referred to as treatment measures).The results of network meta-analysis suggested:①in terms of efficacy:when PASI75 and PASI100 were used as the outcome indicators to evaluate the efficacy,the results of network meta-analysis indicated that the efficacy in the anti-IL-17 antibody group was markedly superior to the placebo group and the etanercept group.The PASI75 and PASI100 index of the high-dose group of secukinumab(300mg),the high-dose group of brodazumab(210mg),and the high-frequency group of ixekizumab(80mg Q2W)were significantly higher than low-dose group or low-frequency group.Based on the PASI75 index,the highest ranking of SUCRA was the ixekizumab 80mg Q2W group;based on the PASI100 index,the highest ranking of SUCRA was brodazumab 210mg group;②In terms of safety:taking the incidence of adverse events and the incidence of serious adverse events as outcome indicators of safety,the results of the network meta-analysis showed that the incidence of adverse events of secukinumab 150mg,ixekizumab 80mg Q4W/Q2W,brodazumab 210mg was significantly higher than that in the placebo group,but there was no statistical difference in the incidence of serious adverse events among the treatment measures.Based on the incidence of adverse events,the lowest ranking of SUCRA was ixekizumab 80mg Q2W in safety;Based on the incidence of serious adverse events,the lowest ranking of SUCRA was ixekizumab 80mg Q4W in safety.Conclusions1.Anti-IL-17 antibodies are highly effective in the short-term treatment of moderate to severe plaque psoriasis and are generally safe.2.In terms of improving psoriasis skin lesions,high-dose or high-frequency anti-IL-17 antibody treatment is more effective than low-dose or low-frequency application,but the safety is equivalent.3.Anti-IL-17 inhibitors have better efficacy than etanercept regardless of the using dosage and frequency,but there is no significant difference in safety between two.