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Objective A plethora of patients diagnosed with ulcerative colitis (UC) will develop an episode of moderate to severe UC flare during the disease course, which may require hospitalisation. Rescue therapy after intravenous corticosteroid failure traditionally includes infliximab (IFX) or ciclosporin; however, many patients admitted with a moderate to severe UC flare have prior IFX exposure, limiting its utility. Janus kinase inhibitors, particularly upadacitinib, have shown promise in observational studies, but data remain limited.Design/methods We conducted a retrospective, single-centre observational study of adults admitted with moderate to severe UC flare and previously exposed to IFX who received upadacitinib 45 mg/day as inpatients between January 2023 and June 2025. The primary outcomes were colectomy-free survival at week 12 and clinical remission at discharge, defined by a simple clinical colitis activity index (SCCAI) score ≤2. Secondary outcomes included clinical response, biochemical remission evaluated by faecal calprotectin (FCP) and C reactive protein (CRP), endoscopic response, treatment persistence, adverse events and colectomy rates up to 12 months.Results We recruited 24 patients. The mean age was 44.3 years (±14.5) with a median disease duration of 5 years (IQR 2.6–14.8). Colectomy-free survival at week 12 was 91.7%, with colectomies performed on days 8 and 16 post-initiation. Among the 12 patients with 12-month follow-up, no further colectomies occurred. SCCAI improved from a median value of 9 on admission to 2 at week 12. 9 out of 22 patients (41%) on upadacitinib achieved biochemical remission at week 12 with FCP below 150 ug/g and CRP below 5 mg/L. The UC endoscopic index of severity was also evaluated with 4 patients achieving endoscopic response (66.7%) at week 12. No major adverse events occurred, including thromboembolic events and malignancies; minor adverse events included acne, flu-like symptoms and transient abnormal liver function tests.Conclusion Upadacitinib shows promise as a potential rescue option in moderate to severe UC among patients previously exposed to IFX. Randomised controlled trials are needed to confirm its efficacy and safety in both IFX-naïve and previously exposed populations.