IntroductionUstekinumab is an effective biologic therapy for inflammatory bowel disease (IBD), yet many patients experience loss of response requiring dose escalation. Predictors of ustekinumab dose escalation remain poorly defined, particularly across Crohn’s disease (CD) and ulcerative colitis (UC).MethodsWe conducted a retrospective cohort study to includ adult patients with IBD initiated on ustekinumab. The primary outcome was factors associated with dose escalation, defined as shortening ustekinumab maintenance interval to every 4 weeks, analyzed separately for CD and UC via multivariable logistic regression. The secondary outcome assessed predictors of time to escalation among CD patients using multivariable linear regression.ResultsA total of 206 patients were included (CD: 165, UC: 41). Dose escalation occurred in 69 (41.8%) of CD and 14 (34.1%) of UC patients. In CD, prior biologic use (OR 3.05; 95% CI: 1.31–7.14; p = 0.01) and prior immunomodulator use (OR 2.07; 95% CI: 1.00–4.29; p = 0.05) were significantly associated with escalation. Longer disease duration was also observed in escalated patients (median 6 vs. 4 years, p = 0.003). In UC, none of the evaluated variables predicted escalation. Median time to escalation was 9 months (IQR 3–18) in CD and 4.5 months (IQR 2–12.8) in UC. No predictors were significantly associated with time to escalation in CD subgroup analysis.ConclusionPrior biologic exposure, immunomodulator use, and longer disease duration predict ustekinumab dose escalation in CD but not in UC, highlighting disease-specific differences in therapeutic needs. These findings support tailored dose optimization strategies in IBD and underscore the need for prospective studies incorporating therapeutic drug monitoring and standardized escalation protocols.