Prevalence, patient characteristics, and outcomes of high-dose upadacitinib in inflammatory bowel disease.

Abstract

Background: Off-label high-dose upadacitinib (UPA) may be necessary for select inflammatory bowel disease (IBD) patients.

Objectives: To evaluate the rates, patient characteristics, and outcomes of extended induction and high-dose UPA maintenance in IBD.

Design: We conducted a two-center, retrospective cohort study of IBD patients treated with UPA from January 1, 2022, to March 1, 2025.

Methods: Extended induction was defined as receiving UPA 45 mg for 16 weeks in ulcerative colitis (UC) and 24 weeks in Crohn's disease (CD). High-dose maintenance was defined as continuing UPA 45 mg after induction/extended induction. Primary outcomes included rates and characteristics of high-dose maintenance. Secondary outcomes included clinical response (CR), steroid-free clinical remission (SFCR), endoscopic remission (ER), and adverse events, comparing standard and high-dose UPA groups.

Results: Among 128 patients (46.9% CD, 48.4% UC, 4.7% IBD-unclassified), 51.6% (n = 66) received extended induction and 34.4% (n = 44) continued high-dose UPA maintenance. On multivariate analysis, UPA high-dose maintenance patients were more likely to have a higher number of prior biologic exposures (odds ratio (OR) 1.84, 95% confidence interval (CI) 1.05-3.19, p = 0.022) and concomitant biologic use (OR 6.18, 95% CI 1.15-33.18, p = 0.034). In the high-dose maintenance group, rates of CR were 73.7%, SFCR 65.8%, and ER 36.7%. Adverse event rates were similar between high- and standard-dose maintenance groups (25% vs 26.8%), with no cases of herpes zoster, venous thromboembolism, or major adverse cardiovascular events.

Conclusion: One-third of patients remained on high-dose UPA maintenance, reflecting more refractory disease and modest response rates. Treatment was generally well tolerated. Larger, long-term studies are needed to validate safety.