A meta-analysis of the efficacy and safety of Janus kinase inhibitors in patients with ulcerative colitis.

Abstract / Summary

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing intestinal inflammation and substantial impairment of quality of life. Janus kinase (JAK) inhibitors are orally administered small-molecule agents that interfere with intracellular cytokine signaling pathways central to UC pathogenesis. This systematic review and meta-analysis aimed to assess the therapeutic benefits and safety profile of JAK inhibitors in adults with moderate-to-severe UC. A systematic literature search was conducted in PubMed (from inception to November 2025), Embase, the Cochrane Library, and Web of Science to identify placebo-controlled RCTs evaluating JAK inhibitors in adult patients with UC. The primary efficacy outcomes were clinical remission and clinical response. Secondary outcomes included endoscopic remission, endoscopic response, and mucosal healing. Safety was assessed by the incidence of any adverse events (AEs). Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects models as appropriate. Statistical heterogeneity was evaluated using the I2 statistic, and subgroup analyses were performed according to treatment phase. Nine publications encompassing 14 placebo-controlled RCT datasets met the inclusion criteria. Compared with placebo, JAK inhibitors significantly increased rates of clinical remission (RR = 2.48, 95% CI: 1.64-3.73) and clinical response (RR = 2.53, 95% CI: 1.73-3.70), although moderate-to-high heterogeneity was observed. Endoscopic outcomes were also markedly improved, with higher rates of endoscopic remission (RR = 3.52, 95% CI: 2.55-4.86) and mucosal healing (RR = 2.60-2.79 across models). Safety analyses demonstrated no significant difference in the overall incidence of adverse events between JAK inhibitors and placebo. Subgroup analyses revealed consistent efficacy during both induction and maintenance phases, with comparable safety profiles across treatment periods. JAK inhibitors provide significant improvements in both clinical and endoscopic outcomes for patients with moderate-to-severe UC without increasing the overall risk of adverse events in short-term trials. These findings support the clinical utility of JAK inhibitors in UC management, while highlighting the need for long-term studies to better characterize rare and delayed safety signals.

Related Clinical Guidelines