Upadacitinib for Acute Severe Ulcerative Colitis: Real-World Tertiary Care Outcomes

Background Acute severe ulcerative colitis (ASUC) affects up to 25% of patients with ulcerative colitis. Despite intravenous (IV) corticosteroids as first-line therapy, 30-40% require rescue treatment and up to 40% undergo colectomy within one year. Upadacitinib (UPA) has shown ability to induce rapid response in moderate-severe UC, but real-world data in ASUC remain limited. We aimed to describe outcomes of UPA initiation for ASUC across Mayo Clinic sites. Methods We conducted a descriptive study of 23 adults hospitalized with ASUC between 2022-2025 at Mayo Clinic. Patients with their first ASUC admission who were started on UPA were included. All patients received IV methylprednisolone (40-60 mg/day) within 24-48 hours of admission, followed by UPA initiation (inpatient or shortly after discharge). Clinical, laboratory, and treatment data were extracted from electronic medical records. Outcomes included colectomy during admission and colectomy within one year. Descriptive statistics were done using Microsoft Excel. Results Twenty-three patients received UPA (median age 35 years; 88% pancolitis; 4% PSC). Out of the 23, 18 were started on UPA during the ASUC admission. Before admission, 10 patients (43%) were receiving corticosteroids, three (13%) were on mesalamine, one (4%) on azathioprine, and 12 (52%) were on biologic therapy; four patients (17%) were already on lower dose UPA maintenance. The median number of prior advanced therapies was two (range 1-4). Admission labs showed a mean CRP of 56.3 mg/L (SD 44.9) and fecal calprotectin of 2521.9 µg/g (SD 783.9). Patients received IV corticosteroids for a mean of 3.7 days (SD 1.1), and UPA was initiated at a median of hospital day 3 (IQR 4). 2/18 patients (11.1%), who were started on UPA inpatient, required colectomy during admission. Of the 23 patients who received UPA during hospitalization or shortly after discharge, one year colectomy rate was 4/23 (17%). Conclusions In this cohort, initiation of UPA during hospitalization or shortly after discharge for ASUC was feasible and was associated with lower colectomy rates compared with published outcomes for patients treated with infliximab or cyclosporine, both during hospitalization (11.1% vs. 21% vs. 25%) and at one year (17% vs. 35% vs. 45%). These findings suggest that UPA may serve as an effective rescue option for hospitalized ASUC patients, particularly when rapid control of inflammation is needed. Larger prospective studies are warranted to confirm these observations and to define optimal timing, patient selection, and long-term safety in the ASUC setting.