S1828 Predictors of Response to Ustekinumab and Identification of Factors Associated With Dose Escalation in Patients With Inflammatory Bowel Disease

Introduction: Dose escalation of ustekinumab 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 ustekinumab from 2016–2022 with ≥1 year of follow-up across 5 tertiary centers. The primary outcome was dose escalation, defined as shortening the maintenance interval and/or additional IV induction. Patients were stratified by IBD subtype and prior advanced therapy (AT) exposure. Multivariable regression identified factors associated with dose escalation and remission. Results: We identified 1,202 patients initiating ustekinumab (58% women, mean age 41.7 years), 80% with CD, 18% UC, and 13% AT–naïve. In CD, ileocolonic disease (58%), inflammatory phenotype (50%), perianal involvement (26%), and prior surgery (52%) were common. AT–exposed patients had higher rates of prior surgery (55% vs 28%) and perianal disease (28% vs 11%) than AT–naïve patients. In UC, 61% had pancolitis. At ustekinumab initiation, inflammatory markers (mean CRP 10.3 mg/L, fecal calprotectin 432.6 μg/g) were elevated and 42% were on corticosteroids. Within one year, 52% required escalation—more frequently in AT–exposed patients (54%) than AT–naïve (39%). Most escalated to q6 wks (53%) or every 4 weeks (46%); repeat IV induction was rare (6%), especially in AT–naïve (1%). Common reasons for escalation included persistent symptoms (52%), low drug levels (56%), and endoscopic activity (25%). At 12 months, 960 patients remained on ustekinumab, with higher persistence in AT–naïve patients (88% vs 83%). Clinical remission was achieved in 70% of AT–naïve and 57% of AT–exposed patients. Among those with endoscopic data, mucosal healing was more frequent in AT–naïve (68%) vs AT–exposed (41%). Dose escalation was independently associated with prior AT exposure (aOR 2.00, 95% CI 1.34–2.99) and UC/IBD-U subtype (aOR 1.81, 95% CI 1.26–2.61). In CD, AT exposure and higher weight were linked to escalation; in UC/IBD-U, higher weight was associated. Conclusion: Over half with IBD initiating ustekinumab required dose escalation, particularly those with prior AT exposure, UC, or higher weight. Despite this, ustekinumab was associated with high treatment persistence and favorable clinical and endoscopic outcomes.