Comparative Efficacy And Safety Of Biosimilars,Biologics And Janus Kinase Inhibitors For Active Crohn Disease

Objective: Crohn disease（CD）is a recurrent systemic inflammatory disease characterized by invasion of the gastrointestinal tract,along with extraintestinal manifestations and associated immune dysfunction.With the introduction of several target-specific biologics,biosimilars,and Janus kinase inhibitors,the precise positioning of different therapeutic agents will be an important issue facing clinicians.The co-occurrence and burst networks were employed to understand the evolution of CD management and the emerging events in a given period.A network meta-analysis based on Bayesian model was subsequently performed to assess the comparative efficacy and safety of various interventions in patients with active CD.Methods: We initially retrieved for all researches on CD management in the Web of Science database from 1992 to 2021,followed by the co-authorship,co-country,keywords co-occurrence and burst,as well as documents co-citation analyses using Citespace software.Pub Med,Embase,Web of Science,the Cochrane Library,CNKI,Wanfang databases and Clinical Trials website were systematically and sequentially searched for randomized controlled trials（RCTs）complying with the criteria.Subsequently,we extracted relevant baseline data and outcomes of interest from the eligible literatures in strict accordance with the standards that have been developed.Primary effectiveness endpoints included induction of remission（CDAI <150 in the induction period）and maintenance of remission（CDAI <150 in the maintenance period）.Secondary efficacy indicators contained induction of response（CDAI-70/100 in the induction period）and maintenance of response（CDAI-70/100 in the maintenance period）;Safety metrics included adverse events（AEs）and infections or serious/severe infections that occurred during treatments.The mixed comparisons of various regimens based on constructed Bayesian model were performed to explore the relative efficacy and safety of these interventions.Sensitivity analysis was eventually applied to test the stability of the results.The PROSPERO registration number is CRD42020187807.Results: A total of 9335 records were downloaded from Web of Science for bibliometric analysis.Following de-duplication and filtering,we carried out visualization of senior authors and most frequently published countries in the field through co-occurrence analyses.Visualizations of research history and research hotspots were achieved using keywords co-occurrence and burst analyses.Core literatures and clusters within the field were finally presented by means of documents co-citation and clustering analyses,respectively.After literature screening and deweighting,31 studies,which contained a total of 34 RCTs,were finally included for network meta-analysis.The results of the Bayesian network analysis demonstrated that infliximab（OR 2.47,95% CrI 1.34-5.01;OR 2.63,95% CrI 1.24-6.14）and adalimumab（OR 2.57,95% CrI 1.51-4.24;OR 2.69,95% CrI 1.38-5.32）were superior to certolizumab pegol and tofacitinib;BI 695501（OR 4.58,95% CrI 1.90-10.99）and CTP13（OR 2.93,95% CrI 1.30-7.72）were more effective in induction of remission compared to placebo（OR 2.90,95% CrI 1.31-7.59）;in terms of maintenance of remission,infliximab（OR 8.24,95% CrI 1.55-40.20）,adalimumab(OR 8.97,95% CrI1.55-45.65,CT-P13（OR 12.45,95% CrI 1.55-79.96）,and ustekinumab（OR 6.98,95%CrI 1.19-35.25）were superior to filgotinib,and CT P13（OR 5.42,95% CrI 1.51-17.33）had a significant superiority over the placebo.Combined with the results of the ranking of the efficacy indicators,it was found that BI 695501 was more favorable in induction of remission and CT-P13 was more preferable in maintenance of remission among all therapeutic regimens.The differences in AEs and infectious events caused by each regimen were not statistically significant.Conclusions: In this study,we systematically reviewed the therapeutic history of CD.In the context of the current availability of multiple treatment options but lack of direct comparisons,we found that biosimilars BI 695501 and CT-P13 showed significant superiority in the induction and maintenance of remission for CD,respectively,by means of network comparisons based on Bayesian model.More attention should be paid to the efficacy and safety evaluation of biosimilars in the future.Cost-effectiveness analysis of biosimilars and corresponding switching treatments is also warrant.