Comparative effectiveness of tofacitinib versus upadacitinib for the treatment of acute severe ulcerative colitis

Abstract

Background & aims: Tofacitinib and upadacitinib are Janus kinase (JAK) inhibitors that are increasingly used for the treatment of acute severe ulcerative colitis (ASUC). However, comparative analyses of safety and effectiveness have not been performed for their use in this setting.

Methods: This multicenter, retrospective study enrolled hospitalized adult patients treated with tofacitinib or upadacitinib for ASUC between January 2019 and June 2024. The main outcomes were clinical response, clinical remission, and colectomy-free survival. Propensity-adjusted analyses using inverse probability treatment weighting, and double robust estimations were used to control for confounding factors.

Results: In total, 111 patients (60 tofacitinib, 51 upadacitinib) were enrolled across 23 international centers. JAK inhibitors were used to induce response in 86 patients (77%) and used to maintain response after adequate intravenous steroid response in 25 (23%). The median follow up was 31 weeks (interquartile range, 13-64 weeks). Between days 3 and 7 after treatment initiation, upadacitinib was associated with greater response rates (84% vs 54%; P = .02), but response/remission was comparable at day 98 (45%/36% vs 55%/48%) and day 182 (29/29% vs 39/34%). Sub-analyses for JAK inhibitor use as salvage therapy (tofacitinib [n = 35] vs upadacitinib [n = 31]) showed similar effectiveness outcomes across both groups. The probabilities of colectomy-free survival at days 98 and 182 for tofacitinib and upadacitinib were 79% and 75% and 80% and 78%, respectively, with no significant differences in the comparison of survival curves (P = .99). Treatment failure rates (where JAK inhibitors were used to maintain remission) were similar at days 98 and 182. The frequency of adverse events was comparable.

Conclusion: Tofacitinib and upadacitinib appear to have similar effectiveness and safety profiles when used for the treatment of ASUC.

Keywords: Acute Severe Ulcerative Colitis; Colectomy; Effectiveness; Janus Kinase Inhibitors; Tofacitinib; Ulcerative Colitis; Upadacitinib.