Predictors of Ustekinumab Dose Escalation in Patients with Inflammatory Bowel Disease: a multicenter retrospective cohort study

Abstract Background Dose escalation of ustekinumab (UST) for inflammatory bowel disease (IBD) is common. We aimed to determine the proportion of patients with Crohn’s disease (CD) and ulcerative colitis (UC) who required dose escalation after intravenous induction, and to identify clinical factors associated with escalation. Methods We performed a multicenter retrospective cohort study of adults with IBD initiating UST from 2016–2022 with ≥1 year of follow-up across four tertiary centers. The primary outcome was dose escalation, defined as shortening the maintenance interval and/or additional IV induction. Multivariable regression identified factors associated with UST dose escalation and clinical remission. Results Among 1,202 patients initiating UST (80% CD, 18% UC, 2% IBD-U), 88% had prior advanced therapy exposure. UST dose escalation occurred in 52% (median time: 172 vs 197 days for therapy-exposed vs naïve). Escalation was associated with prior advanced therapy (aOR 1.78, 95% CI 1.24–2.58), UC/IBD-U (aOR 1.78, 95% CI 1.31–2.43), and higher body weight. At 12 months, UST persistence was high (83% exposed, 88% naïve). Clinical remission was achieved in 67% of naïve vs 53% of exposed patients, with higher rates of corticosteroid discontinuation and mucosal healing among naïve individuals. Prior therapy exposure, corticosteroid use, opioid use, and perianal disease (in CD) predicted lower remission rates. Conclusion UST demonstrates high persistence and favorable outcomes in IBD; however, more than half of patients undergo dose escalation in real-world practice. Advanced therapy exposure, UC subtype, and higher body weight are key predictors of escalation, underscoring the importance of individualized dose optimization in clinical practice.