Effectiveness and safety of upadacitinib for inflammatory bowel disease: A systematic review and meta-analysis of RCT and real-world observational studies

Background: Upadacitinib, a novel and selective inhibitor of Janus kinase 1, has demonstrated promising efficacy in managing inflammatory bowel disease (IBD). In this systematic review and meta-analysis, our primary aim was to comprehensively assess the therapeutic effectiveness and safety profile of upadacitinib in the treatment of patients with IBD. Methods: We conducted an extensive literature search across prominent databases, including Medline, Embase, Web of Science, and Cochrane Central, to identify pertinent studies providing insights into the efficacy and safety of upadacitinib in IBD. The primary endpoint was the achievement of clinical remission, while secondary endpoints encompassed clinical response, endoscopic response, endoscopic remission, and the evaluation of adverse events (AEs). Results: In this meta-analysis of nine studies, we categorized results by study type. Clinical remission rates were: RCTs 36 % (95 % CI = 30-42 %), real-world studies 25 % (95 % CI = 1-49 %), retrospective studies 40 % (95 % CI = 24-56 %), cohort studies 55 % (95 % CI = 25-85 %). Clinical response rates were: RCTs 61 % (95 % CI = 55-67 %), real-world studies 42 % (95 % CI = 14-70 %), cohort studies 65 % (95 % CI = 57-73 %). Endoscopic remission rates were: RCTs 19 % (95 % CI = 15-24 %), cohort studies 29 % (95 % CI = 5-52 %). Endoscopic response rates were: RCTs 41 % (95 % CI = 36-47 %), cohort studies 57 % (95 % CI = 31-83 %). Incidence rate for any AEs: IBD 69 % (95 % CI = 63-76 %), UC 65 % (95 % CI = 57-74 %), CD 75 % (95 % CI = 67-82 %). Conclusion: Cumulative data from real-world studies and trials confirm the efficacy of upadacitinib in IBD induction and maintenance, with consistent safety. However, further long-term studies are needed to understand its sustained effectiveness and safety.