Effectiveness and Safety of Janus Kinase Inhibitors in Acute Severe Ulcerative Colitis: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Janus kinase (JAK) inhibitors have been reported to be useful in acute severe ulcerative colitis (ASUC). We performed a systematic review and meta-analysis to assess their effectiveness and safety in ASUC.

METHODS

Electronic databases (PubMed, Embase, and Scopus) were searched on December 17, 2025, to identify reports about using JAK inhibitors in ASUC. We extracted data concerning clinical response, remission, colectomy, and adverse events with the use of JAK inhibitors in ASUC. Pooled clinical response rates, remission rates and colectomy were calculated at short-term (<30 days), intermediate (<3 months) and long-term (3-12 months) therapy. The quality of studies was assessed using Joanna Briggs' tools.

RESULTS

A total of 35 studies (664 patients) were included. In the short term (<1 month), the pooled clinical response and colectomy rate with tofacitinib was 77.9% (95% confidence interval [CI], 67.1%-86%) and 11.5% (95% CI, 7.1%-18.4%), whereas for upadacitinib, it was 86.5% (95% CI, 72.3%-94.1%) and 11.2% (95% CI, 7.2%-16.9%), respectively. In the intermediate term (<3 months), the pooled clinical response, remission, and colectomy rates with tofacitinib and upadacitinib were 57.2% (95% CI, 49.2%-64.8%), 37.3% (95% CI, 28.1%-47.5%), 16.1% (95% CI, 10.9%-23.1%), and 56.1% (95% CI, 39.3%-71.7%), 47.4% (95% CI, 37.6%-57.4%), 21.2% (95% CI, 15.8%-27.7%), respectively. In the long term (3-12 months), the pooled clinical response, remission, and colectomy rates with tofacitinib and upadacitinib were 41.4% (95% CI, 34.4%-48.8%), 33.8% (95% CI, 28.4%-39.5%), 22.6% (95% CI, 17.5%-28.6%), and 35.1% (95% CI, 21.1%-52.2%), 37.5% (95% CI, 19.1%-60.4%), 23.4% (95% CI, 17.1%-31.4%), respectively. The adverse events reported were venous thromboembolism (2.2%; 95% CI, 1.1%-4.7%), major adverse cardiovascular events (0.7%; 95% CI, 0.1-10.3%), and herpes zoster (3.4%; 95% CI, 1.9%-6.1%). There was no difference in the effectiveness of high-dose as compared with standard-dose tofacitinib.

CONCLUSIONS

JAK inhibitors are effective and safe in the treatment of ASUC as an adjunct to intravenous corticosteroids and as rescue therapy. Both tofacitinib and upadacitinib were associated with similar outcomes in ASUC. Randomized controlled trials evaluating the role of JAK inhibitors as co-therapy with corticosteroids and as a salvage therapy agent in corticosteroid non-responsive ASUC are required.