Network Meta-Analysis Of Efficacy And Safety Of Drugs For The Treatment Of Moderate To Severe Ulcerative Colitis

Objective: To compare the efficacy and safety of aminosalicylic acid agents,glucocorticoids,immunosuppressive agents,biological agents,and small molecule drugs alone or in combination in the treatment of moderate to severe Ulcerative Colitis by network Meta-analysis.Methods: Pub Med,Embase,The Cochrane Library,and Web of science were searched by computer to collect the literatures about aminosalicylic acid preparations,glucocorticoids,immunosuppressants,biological agents,and small molecule drugs used alone or in combination in the treatment of UC.The search time was from the establishment of the database to December 31,2022.The literature was screened and the data were extracted according to the predefined inclusion and exclusion criteria.The risk of bias of the included literature was assessed by the Cochrane risk of bias assessment tool.Stata 17.0 software was used to test the heterogeneity of the included studies and conduct a direct meta-analysis,draw network evidence diagrams of seven outcome indicators including clinical response rate in the induction phase,clinical remission rate in the induction phase,mucosal healing rate in the induction phase,clinical remission rate in the maintenance phase,mucosal healing rate in the maintenance phase,incidence of adverse events and serious adverse events after different interventions in the treatment of moderate to severe UC.The consistency of the parts that formed the closed loop was detected,and then the network Meta-analysis was performed,and the SUCRA probability ranking map and the "comparison-specific" funnel plot were drawn.Finally,subgroup analysis was performed on the outcome indicators of the maintenance period according to the experimental design scheme,and the network evidence diagram and SUCRA probability ranking diagram of subgroup analysis were drawn.Results: A total of 18 articles(a total of 22 RCTS)were included,including 7873 patients with moderate to severe UC.The results of network Meta-analysis showed that(1 RCT did not conduct network Meta-analysis due to its small sample size):(1)A total of 17 studies reported induction clinical response rates.SUCRA probability ranking results were Upadacitinib > Infliximab/AZA > Infliximab>Ustekinumab > Tofacitinib > Ozanimod > Vedolizumab > Golimumab > Adalimumab >Placebo.(2)A total of 16 studies reported clinical remission rates during the induction phase.SUCRA probability ranking results were Upadacitinib> Infliximab> Ozanimod >Ustekinumab > Tofacitinib> Golimumab> Vedolizumab > Adalimumab > Placebo.(3)A total of 16 studies reported the rate of endoscopic improvement during the induction period.SUCRA probability ranking results were Upadacitinib >Infliximab/AZA > Infliximab > Ozanimod > Tofacitinib > Ustekinumab> Golimumab >Vedolizumab> Adalimumab > Placebo.(4)A total of 13 studies reported clinical remission rates in maintenance phase.SUCRA probability ranking results were Upadacitinib > Tofacitinib > Vedolizumab>Infliximab> Ozanimod> Adalimumab> Ustekinumab> Golimumab> Placebo.(5)A total of 14 studies reported endoscopic improvement rate in maintenance period.SUCRA probability ranking results were Upadacitinib> Tofacitinib> Infliximab>Vedolizumab> Ustekinumab > Golimumab > Ozanimod> Adalimumab > Placebo.(6)A total of 15 studies reported the incidence of AE.SUCRA probability ranking results were Ozanimod> Golimumab> Infliximab/AZA> Infliximab> Upadacitinib >Adalimumab> Placebo> Ustekinumab > Tofacitinib > Vedolizumab.(7)A total of 16 studies reported the incidence of SAE,and all comparisons were not statistically significant.SUCRA probability ranking results were Infliximab/AZA >Golimumab > Placebo > Adalimumab > Ustekinumab> Infliximab> Vedolizumab >Tofacitinib > Ozanimod > Upadacitinib.Conclusions:(1)Upadacitinib may have the best efficacy during the induction and maintenance periods,with the lowest SAE rate,and be the most comprehensively effective intervention.(2)Vedolizumab may have the best safety profile.(3)Infliximab combined with AZA may improve efficacy and reduce safety.