Upadacitinib versus Tofacitinib in the Management of Ulcerative Colitis: A Systematic Review and Meta-Analysis.

Introduction: Upadacitinib and tofacitinib, oral Janus kinase inhibitors, have demonstrated efficacy and safety in ulcerative colitis (UC) in clinical trials. However, real-world comparative data are limited. We conducted a systematic review and meta-analysis of studies directly comparing upadacitinib to tofacitinib in UC management. Methods: We conducted a systematic search of multiple databases through August 2025 for studies comparing upadacitinib and tofacitinib for UC management. The primary outcome was steroid-free clinical remission (SFCR) at weeks 8-14. Secondary outcomes included SFCR at later timepoints, clinical and endoscopic remission, biochemical remission, treatment discontinuation, colectomy, and safety. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random effects model. Heterogeneity was assessed using the I 2% statistic. Results: Ten retrospective studies with 2,021 patients (879 upadacitinib and 1,142 tofacitinib) were analyzed. Upadacitinib was associated with significantly higher SFCR at weeks 8-14 (OR 1.98; 95% CI: 1.32-3.97; I 2 = 30%), 48-60 weeks (OR 2.32; 95% CI: 1.50-3.58; I 2 = 0%), and at the end of study follow-up (OR 3.60; 95% CI: 1.73-3.92; I 2 = 0%). Rates of endoscopic and biochemical remission did not differ significantly. Treatment discontinuation was less frequent with upadacitinib (OR 0.51; 95% CI: 0.34-0.77; I 2 = 22%). Overall safety was comparable, except for higher odds of acne with upadacitinib (OR 4.30; 95% CI: 1.86-9.95; I 2 = 0%). Conclusion: Upadacitinib may be more effective than tofacitinib in achieving and sustaining SFCR, with better treatment persistence and similar overall safety. Larger, prospective head-to-head trials are needed to validate these findings.