Long-Term Real-World Evaluation of Tofacitinib's Effectiveness and Safety in Japan: Insights Into Optimal Timing for...

Tofacitinib (TOF), an oral pan-Janus kinase (JAK) inhibitor, is a therapeutic option for moderate to severe ulcerative colitis (UC). While short-term efficacy has been reported, its long-term real-world outcomes-particularly in Asian populations-and optimal dose reduction timing are incompletely understood.

This single-center, retrospective study included 63 patients with UC treated with TOF between October 2018 and April 2025. Clinical outcomes-response, remission, steroid-free remission, and adverse events-were assessed at Weeks 26, 52, and 104. The impact of dose reduction (20-10 mg/day) was analyzed, focusing on endoscopic mucosal healing (Mayo endoscopic subscore 0-1). At Week 26, clinical response and remission rates were 63% and 53%, respectively; 43% of patients achieved steroid-free remission by Week 52, and 41% maintained it at Week 104. Early responders were associated with treatment efficacy in a lower partial Mayo score (OR = 1.724, 95% CI: 0.994-2.988, p = 0.052). Among 26 patients with dose reduction, relapse occurred in 5.6% with mucosal healing versus 62.5% without. Significant factors associated with relapse/exacerbation were TOF dose reduction based on clinical remission alone without endoscopic confirmation (p = 0.003, OR = 5.26) and disease duration (p = 0.019, OR = 0.86). Adverse events were infrequent and manageable, with no malignancies or deaths reported.

TOF demonstrated sustained effectiveness and safety in UC. Mucosal healing was strongly associated with successful dose de-escalation, representing a key treatment target. These findings support treat-to-target strategies incorporating endoscopic assessment to guide TOF dose reduction.