Upadacitinib is Associated With Better Clinical and Biochemical Outcomes Than Tofacitinib in Refractory, Moderate-to-severe Ulcerative Colitis

Background & aims: Comparative data on the effectiveness of tofacitinib (TOFA) and upadacitinib (UPA) in ulcerative colitis (UC) remain limited. We conducted a multicenter, retrospective cohort study to evaluate and compare the short- and mid-term effectiveness of TOFA and UPA in bio-experienced, moderate-to-severe UC. Methods: Inverse probability weighting analysis was performed for demographics, baseline Mayo score, and baseline C-reactive protein [CRP] and fecal calprotectin [FCal], as well as concomitant corticosteroid use between the 2 treatment groups. The coprimary outcome was week 12 and 24 corticosteroid-free remission (CSFR) defined as clinical remission (CR) and CRP ≤5 mg/L, as well as not receiving steroids ≥30 days. We also assessed the rate of CR and biochemical remission (defined as CRP ≤5 mg/L and FCal ≤ 250 μg/g) during the first 6 months of therapy. Results: A total of 350 patients with UC (246 TOFA, 104 UPA; mean age, 38.6 ±13.8 years; median follow-up, 11 months) were enrolled in the study. The likelihood of achieving CSFR at both week 12 (adjusted odds ratio [aOR], 2.2; 95% confidence interval [CI], 1.2-4.1) and week 24 (aOR, 2.2; 95% CI,1.2-3.9) was found to be significantly higher in patients treated with UPA than in patients receiving TOFA. UPA was also associated with around 2-fold higher odds of reaching both CR (95% CI, 1.3-4.3; 95% CI, 1.0-3.4) and biochemical remission (95% CI, 1.3-4.4; 95% CI, 1.2-4.0) at the same timepoints compared with TOFA. No significant differences were seen in IBD-related hospitalization and early colectomy rates between the 2 treatment groups. No new safety signal was noted. Conclusion: UPA might be associated with better short- and mid-term clinical and biochemical outcomes compared with TOFA in refractory, moderate-to-severe UC.