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.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis (UC); Upadacitinib; Acute Severe Ulcerative Colitis
• Intervention / Treatment: Drug: Upadacitinib

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 81

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Xijing Hospital,Fourth Military Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This is a multicenter, retrospective cohort study conducted at 11 tertiary inflammatory bowel disease (IBD) centers in China from June 2023 to December 2025. A total of 81 patients diagnosed with ASUC according to the modified Truelove and Witts criteria were enrolled. All patients received upadacitinib as first-line or rescue therapy. The study population was categorized into two groups: the first-line therapy group (upadacitinib administered in ASUC patients who had not previously received corticosteroids or biologics during this episode) and the rescue therapy group (including second-line and third-line therapy, defined as upadacitinib initiation after failure of intravenous methylprednisolone or both intravenous methylprednisolone and infliximab).

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ASUC Patients with First-Line Upadacitinib Exposure; This retrospective observational cohort includes patients diagnosed with acute severe ulcerative colitis (ASUC) who received upadacitinib as first-line therapy in routine clinical practice. First-line upadacitinib was defined as administration in ASUC patients who had not previously received corticosteroids or biologics during this episode. All treatment decisions were made by treating clinicians per standard of care; the investigator did not assign or modify any therapeutic interventions, and only retrospectively collected and analyzed clinical outcomes from medical records.	Drug: Upadacitinib; Upadacitinib was administered orally as part of routine clinical care for acute severe ulcerative colitis (ASUC), in accordance with standard clinical guidelines. The induction dose was 45 mg once daily for up to 12 weeks (8 weeks for most patients, extended to 12 weeks for a subset with severe disease), followed by a maintenance dose of 30 mg once daily. All dosing decisions were made by treating clinicians; the investigator did not assign, modify, or control any dosing regimen for research purposes.
ASUC Patients with Rescue Upadacitinib Exposure; This retrospective observational cohort includes patients diagnosed with acute severe ulcerative colitis (ASUC) who received upadacitinib as part of routine rescue therapy (second- and third-line treatment). Second-line rescue therapy was defined as upadacitinib initiation after 3-5 days of intravenous methylprednisolone (40-60 mg/day) with inadequate response. Third-line rescue therapy was defined as upadacitinib use following failure of both intravenous methylprednisolone and infliximab during the same ASUC episode. All treatment decisions were made by treating clinicians in accordance with standard of care; the investigator did not assign, modify, or control any therapeutic interventions, and only retrospectively collected and analyzed clinical outcomes from medical records.	Drug: Upadacitinib; Upadacitinib was administered orally as part of routine clinical care for acute severe ulcerative colitis (ASUC), in accordance with standard clinical guidelines. The induction dose was 45 mg once daily for up to 12 weeks (8 weeks for most patients, extended to 12 weeks for a subset with severe disease), followed by a maintenance dose of 30 mg once daily. All dosing decisions were made by treating clinicians; the investigator did not assign, modify, or control any dosing regimen for research purposes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical-endoscopic remission rate at 12 weeks	Clinical remission is defined as a total Mayo score ≤ 2 with no subscore > 1 and a rectal bleeding subscore of 0; endoscopic remission is defined as a Mayo endoscopic subscore ≤ 1 without mucosal friability.Clinical-endoscopic remission requires achievement of both clinical and endoscopic remission, assessed at 12weeks after upadacitinib initiation.	12 weeks after upadacitinib initiation
Colectomy-free rate within 90 days	The proportion of ASUC patients who did not undergo colectomy within 90 days after the initiation of upadacitinib treatment	90 days after upadacitinib initiation

Secondary Outcome Measures

Outcome Measure	Time Frame
Patient-Reported Outcomes-2 (PRO2) score at week 1	1 week after upadacitinib initiation
Clinical response rate at weeks 8 and 12	8 weeks and 12 weeks after upadacitinib initiation
Clinical remission rate at weeks 8 and 12	8 weeks and 12 weeks after upadacitinib initiation
Corticosteroid-free clinical remission rate at weeks 8 and 12	8 weeks and 12 weeks after upadacitinib initiation
Endoscopic response rate at week 12	12 weeks after upadacitinib initiation
Endoscopic remission rate at week 12	12 weeks after upadacitinib initiation
Adverse events (AEs) rate	From upadacitinib initiation to study completion

Collaborators and Investigators

• Sponsor: Xijing Hospital of Digestive Diseases

Publications and helpful links

General Publications

• Gisbert JP, Chaparro M. Acute severe ulcerative colitis: State of the art treatment. Best Pract Res Clin Gastroenterol. 2018 Feb-Apr;32-33:59-69. doi: 10.1016/j.bpg.2018.05.007. Epub 2018 May 12.
• Gisbert JP, Chaparro M. Janus kinase inhibitors in the management of acute severe ulcerative colitis: a comprehensive review. J Crohns Colitis. 2025 Feb 4;19(2):jjaf021. doi: 10.1093/ecco-jcc/jjaf021.

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2023
• Primary Completion (Actual): March 3, 2026
• Study Completion (Actual): March 3, 2026

Study Registration Dates

• First Submitted: March 4, 2026
• First Submitted That Met QC Criteria: March 13, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative; upadacitinib
• Other Study ID Numbers: KY20252556-F-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No