Abstract Background Ustekinumab is an effective biologic therapy for inflammatory bowel disease (IBD), yet many patients experience loss of response requiring dose escalation (1). Predictors of ustekinumab dose escalation remain poorly defined, particularly across Crohn’s disease (CD) and ulcerative colitis (UC) (2). Current literature demonstrates variable approaches to managing loss of response to ustekinumab, with limited standardized guidance on dose optimization strategies (3). This study aims to evaluate clinical outcomes and predictive factors supporting ustekinumab dose escalation strategies in IBD patients with loss of response or suboptimal outcomes. Methods We conducted a retrospective cohort study between 2019 and 2024. Study included 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. Results A 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 (figure 1). 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 (figure 1). Conclusion Prior 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. References: 1. Panaccione R, Lee WJ, Clark R, Kligys K, Campden RI, Grieve S, Raine T. Dose Escalation Patterns of Advanced Therapies in Crohn’s Disease and Ulcerative Colitis: A Systematic Literature Review. Adv Ther. 2023 May;40(5):2051-2081. doi: 10.1007/s12325-023-02457-6. Epub 2023 Mar 17. PMID: 36930430; PMCID: PMC10129944. 2. Gisbert JP, Chaparro M. Predictors of Primary Response to Biologic Treatment Anti-TNF, Vedolizumab, and Ustekinumab in Patients With Inflammatory Bowel Disease: From Basic Science to Clinical Practice. J Crohns Colitis. 2020 Jun 19;14(5):694-709. doi: 10.1093/ecco-jcc/jjz195. PMID: 31777929. 3. Rehman MEU, Tahir A, Hussain A, Ali A, Bin Gulzar AH, Khan AQ, Sajjad M, et al. Efficacy of Dose Escalation of Ustekinumab in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. Med Princ Pract. 2025;34(3):226-237. doi: 10.1159/000543831. Epub 2025 Feb 3. PMID: 39900017; PMCID: PMC12133129 Conflict of interest: Dr. Shehab, Mohammad: No conflict of interest Alrashed, Fatema: No conflict of interest Almajdi, Anwar: No conflict of interest Abdullah, Israa: No conflict of interest
Shehab et al. (Thu,) studied this question.