Effectiveness and Safety of Upadacitinib for Acute Severe Ulcerative Colitis

A Comparative Retrospective Observational Study of the Effectiveness and Safety of Upadacitinib as First-Line and Rescue Therapy in Acute Severe Ulcerative Colitis

The aim of this retrospective observational study is to investigate and compare the real-world effectiveness and safety of upadacitinib when used as first-line exposure versus rescue exposure in patients with acute severe ulcerative colitis (ASUC).

The key questions to be addressed are:

In patients with ASUC, does upadacitinib administered as first-line induction exposure result in higher rates of colectomy-free survival, clinical remission, and endoscopic healing compared with its use as rescue exposure following failure of conventional or biologic therapies? What are the differences in the incidence, type, and severity of adverse events between these two real-world treatment exposure patterns?

The researchers will conduct a retrospective analysis of medical records and electronic health data from patients diagnosed with ASUC who received upadacitinib either as part of routine first-line clinical care or routine rescue clinical care. All treatment decisions were made by treating clinicians per standard of care; the investigator did not assign or modify any therapeutic interventions. Data will be collected during a defined follow-up period to compare the real-world effectiveness and safety profiles of the two treatment exposure strategies.

This is a retrospective observational cohort study. All interventions described are part of routine clinical care for acute severe ulcerative colitis (ASUC). Treatment decisions were made by treating clinicians per standard of care; the investigator did not prospectively assign, modify, or control any therapeutic interventions. Participants did not receive any intervention specifically for the purpose of this study. The study only involves retrospective analysis of existing medical records to compare real-world outcomes between different treatment exposure patterns.

Inclusion Criteria:

1. Patients diagnosed with ASUC according to the modified Truelove and Witts criteria;
2. Patients treated with upadacitinib at 11 tertiary inflammatory bowel disease (IBD) centers in China from June 2023 to December 2025；
3. Patients with complete and available clinical, endoscopic, and follow-up data；
4. Patients for whom the study was approved by the Institutional Research 5.Ethics Committee and conducted in accordance with the Declaration of Helsinki.

Exclusion Criteria:

1. Patients with hemodynamic instability;
2. Patients with obvious liver and kidney function injury: bilirubin,aminotransferase (ALT, AST) exceeded the upper limit of normal by 2 times; eGFR < 60ml/min or dialysis patients;
3. Patients allergic to upadacitinib or its excipients;
4. Patients whose primary disease was gastrointestinal malignancy;
5. Patients currently suffering from serious or uncontrolled underlying diseases of the blood, digestive tract, metabolism, endocrine, lung, heart, nervous system, mental system, etc.;
6. Female patients during pregnancy and breastfeeding (including patients with reproductive needs)；
7. Patients with current infection with infectious diseases (hepatitis B, hepatitis C, syphilis, AIDS, tuberculosis, etc.);
8. Patients with missing key data for outcome assessment;
9. Any other circumstances which, in the opinion of the investigator, would render the subject unfit for study inclusion.