Efficacy and tolerability of janus kinase inhibition strategies for moderate-to-severe Crohn's disease: A systematic review and bayesian network meta-analysis.

BACKGROUND: Crohn's disease is a chronic inflammatory bowel disease with an expanding therapeutic landscape for moderate-to-severe disease. Janus kinase (JAK) inhibitors have emerged as effective oral treatment options by modulating intracellular inflammatory signalling pathways. OBJECTIVES: This systematic review and Bayesian Network meta-analysis aimed to synthesize randomized trial evidence evaluating JAK inhibition strategies in moderate-to-severe Crohn's disease. Given the lack of head-to-head trials, indirect comparisons were considered exploratory. DESIGN: Systematic review and Bayesian network meta-analysis of randomized controlled trials (RCTs). DATA SOURCES AND METHODS: Cochrane Central Register of Controlled Trials, MEDLINE (PubMed), Embase, Scopus, and ClinicalTrials.gov were systematically searched from inception to April 2025. A Bayesian NMA was conducted in R. Hazard ratios (HRs) with 95% credible intervals (CrIs) were estimated. Surface under the cumulative ranking curve (SUCRA) values were calculated to rank interventions across efficacy and safety outcomes. The protocol is registered with PROSPERO. RESULTS: Twelve RCTs comprising 25 treatment arms and 5129 patients were included. The network evaluated upadacitinib across six dosing regimens and filgotinib across two. Upadacitinib 45 mg once daily (OD) showed significant efficacy in achieving clinical remission compared to placebo (HR: 2.47; 95% CrI: 1.51-4.10). For endoscopic remission, upadacitinib 24 mg OD ranked highest, followed by upadacitinib 24 mg BID. For endoscopic response, upadacitinib 24 mg OD ranked highest. No statistically significant differences were observed for clinical response. These estimates were associated with very wide credible intervals indicating statistical imprecision. For safety outcomes, no statistically significant differences were observed among various regimens. For Inflammatory Bowel Disease Questionnaire (IBDQ) ≥ 16, all upadacitinib dosing regimens showed a clinically meaningful response. CONCLUSION: In this NMA, upadacitinib-containing regimens showed the most consistent efficacy signal among evaluated JAK inhibition strategies. However, the evidence network was sparse, limiting the clinical applicability. Treatment rankings should therefore be interpreted as exploratory.