S1568 Efficacy of High- vs Low-Dose Upadacitinib in Treatment of Patients With Crohn’s Disease: A Retrospective Cohort Study

Introduction: Upadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, is utilized in a variety of inflammatory autoimmune disorders, including inflammatory bowel disease. Prospective studies have shown UPA is superior to placebo in achieving clinical and endoscopic response in Crohn’s disease (CD) patients. Following a 12-week induction period, a maintenance dose of either 15 mg or 30 mg daily is recommended, however outcomes data is limited in a real-world setting. In this study, we sought to describe outcomes of CD patients treated with either low- or high-dose UPA during maintenance therapy. Methods: We utilized the TriNetX database to retrospectively analyze data from 470,000 adult CD patients from 1/1/2019–02/14/2025. Patients were required to have at least one encounter for Crohn’s disease (K50) and no history of ulcerative colitis (K51). Patients were also required to have at least 2 entries for UPA (RxNorm 2196092) after initial CD, with the UPA entries separated by at least 12 weeks. The 15 mg cohort was also required to have no entries for 30 mg of UPA. Cohorts were matched for age, race, nicotine dependence, Clostridioides difficile infection, and use of immunosuppressants. Outcomes of intravenous or oral steroid use, rates of low fecal calprotectin (FCP), defined as a value of <250 ug/g, and colectomy were evaluated between 3-18 months after initiation of UPA. Chi square analyses were conducted for binary outcomes. Results: There were 192 patients (mean age 43.9 ± 16.2 yrs; 63.5% women; 82% White) included in each cohort after matching for prior biologic exposure and nicotine use. Patients on a maintenance dose of 15 mg had a higher risk of requiring IV or PO steroids between 3 and 18 months of UPA initiation (HR, 1.43; 95% CI, 1.01–2.04; P = 0.044) compared to those on a 30 mg maintenance dose. There was no difference in colectomy rates between groups (15 mg: 0 pts requiring colectomy; 30 mg: ≤10 pts). There was no difference in rates of low FCP (15 mg: ≤10 pts; 30 mg: 19 pts). Conclusion: We found maintenance treatment with 30 mg of UPA is associated with lower rates of IV or oral corticosteroid use within 18 months of therapy initiation compared to those maintained on a 15 mg dose, while there was no difference in risk of colectomy or low FCP values between the groups. The use of the TriNetX dataset limits the ability to collect patient-reported, endoscopic, and disease severity indices. As such, larger, prospective studies would be important to further elucidate this finding.