Upadacitinib in Patients Hospitalized With Acute Severe Ulcerative Colitis

Acute severe ulcerative colitis (ASUC) is a medical emergency associated with high morbidity and colectomy rates despite standard treatment with intravenous corticosteroids and rescue therapy with biologics such as infliximab. Limitations of current therapies include delayed onset of action, need for intravenous administration, and significant corticosteroid-related toxicity. There remains an unmet need for rapidly acting, effective, and steroid-sparing treatment strategies in the inpatient setting.

Upadacitinib is an oral selective Janus kinase 1 (JAK1) inhibitor approved for the treatment of moderate-to-severe ulcerative colitis. In Phase III trials (U-ACHIEVE and U-ACCOMPLISH), upadacitinib demonstrated rapid onset of action, with clinical improvement observed within days of initiation, as well as favorable corticosteroid-sparing effects. However, its use in hospitalized patients with ASUC has not been systematically evaluated in a prospective clinical study.

This is a single-center, prospective, open-label, single-arm Phase IV clinical trial conducted at the University of California, San Francisco (UCSF). The study will evaluate oral upadacitinib 45 mg once daily as corticosteroid-free induction therapy in adults hospitalized with ASUC. Approximately 50 participants aged 18-75 years with established ulcerative colitis and meeting criteria for ASUC (Mayo score \>10 or Truelove and Witts criteria) will be enrolled.

Participants will receive upadacitinib during hospitalization (target duration 5-7 days) and will be followed for 52 weeks to assess short-term and long-term outcomes. The primary endpoint is treatment failure by Day 14, defined as colectomy or need for rescue therapy with intravenous corticosteroids and/or infliximab. Secondary endpoints include safety outcomes such as serious adverse events, infections, thromboembolic events, and laboratory abnormalities. Exploratory endpoints include colectomy rates at multiple time points, time to colectomy, hospital length of stay, and 30-day readmission rates.

Outcomes in the intervention cohort will be compared to a historical control group of ASUC patients treated at UCSF between March 2022 and June 2025 with infliximab-based regimens with or without corticosteroids. To reduce bias associated with the non-randomized design, propensity score matching and multivariable regression analyses will be used to adjust for baseline differences between groups.

This study aims to generate prospective data on the feasibility, safety, and effectiveness of upadacitinib as a novel corticosteroid-free induction strategy in hospitalized patients with ASUC, with the potential to inform future treatment paradigms and reduce reliance on corticosteroids in this high-risk population.