Real-World Outcomes of Upadacitinib vs Risankizumab Among Anti-Tumor Necrosis Factor-Exposed Patients With Crohn's...

The optimal sequencing of therapy following anti-tumor necrosis factor inhibitor failure in Crohn's disease remains uncertain. We compared the effectiveness of upadacitinib vs risankizumab in patients with active luminal Crohn's disease previously exposed to anti-tumor necrosis factor therapies.

We conducted a retrospective single-center cohort study of adults with Crohn's disease initiating upadacitinib or risankizumab (January 2022-November 2025). The primary outcome was postinduction (week 12-24) corticosteroid-free clinical remission. Secondary outcomes included corticosteroid-free clinical remission at week 52, combined corticosteroid-free clinical and biochemical remission postinduction and at week 52, biomarker and endoscopic changes, treatment persistence, and adverse events. Inverse probability of treatment weighting with additional adjustment for baseline disease severity was used to account for baseline differences; sensitivity analyses included weight truncation and overlap weighting.

Among 175 anti-tumor necrosis factor-exposed patients (risankizumab, n = 115; upadacitinib, n = 60), unadjusted postinduction corticosteroid-free clinical remission occurred in 60% (33/55) of upadacitinib-treated patients and 55% (60/109) of risankizumab-treated patients. After inverse probability of treatment weighting and disease severity adjustment, there was no significant difference in postinduction corticosteroid-free clinical remission (adjusted odds ratio, 1.05; 95% confidence interval, 0.46-2.41) or combined corticosteroid-free clinical and biochemical remission (adjusted odds ratio, 1.14; 95% confidence interval, 0.48-2.72). At week 52, remission estimates were limited by reduced follow-up but were also not significantly different after adjustment. Treatment persistence and serious and infectious adverse event rates were similar between groups after adjustment.

In anti-tumor necrosis factor-exposed patients with active luminal Crohn's disease, upadacitinib and risankizumab achieved similar postinduction remission after adjustment for baseline differences.