Efficacy and Safety of Low-Dose Upadacitinib Combined With Ustekinumab in the Treatment of Refractory Crohn's Disease

NCT07697547 | Completed

• 1 other identifier: SHSY-IEC-6.0/25K32/P01
• Study Type: observational
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

A multicenter retrospective study evaluating the effectiveness and safety of ustekinumab combined with low-dose upadacitinib in patients with refractory Crohn's disease.

Conditions

Inflammatory Bowel Disease (IBD); Crohn's Disease

Keywords

Ustekinumab; Upadacitinib; refractory Crohn's disease

Outcome Measures

Primary Outcomes (1)

• Clinical remission rate at Week 12 to Week 16

  The proportion of patients achieving clinical remission at Week 12 to Week 16 after initiation of low-dose upadacitinib plus ustekinumab combination therapy. Clinical remission is defined as a Harvey-Bradshaw Index (HBI) score \<5, or clinical remission as judged by the treating physician.

  Week 12 to Week 16 after initiation of combination therapy

Secondary Outcomes (2)

• Endoscopic healing rate at Week 12 to Week 24

  Week 12 to Week 24 after initiation of combination therapy

• Endoscopic response rate at Week 12 to Week 24

  Week 12 to Week 24 after initiation of combination therapy

Study Arms (1)

Low-dose upadacitinib plus ustekinumab cohort

Patients with refractory Crohn's disease who received low-dose upadacitinib in combination with ustekinumab in a multicenter retrospective real-world cohort study.

Drug: Upadacitinib; Drug: Ustekinumab (UST)

Interventions

Upadacitinib DRUG

Upadacitinib was administered orally at a low dose of 15 mg/day or 30 mg/day for at least 12 weeks in combination with ustekinumab.

Low-dose upadacitinib plus ustekinumab cohort

Ustekinumab (UST) DRUG

Ustekinumab was administered as intravenous induction based on body weight, followed by subcutaneous maintenance therapy at 90 mg every 8 weeks, in combination with low-dose upadacitinib.

Low-dose upadacitinib plus ustekinumab cohort

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients with refractory Crohn's disease from multiple inflammatory bowel disease centers in China who had prior anti-TNF therapy failure, intolerance, or contraindication and inadequate response to ustekinumab or upadacitinib monotherapy. Eligible patients received low-dose upadacitinib in combination with ustekinumab in routine clinical practice between July 1, 2023 and May 31, 2025, and were included in this retrospective real-world cohort study.

You may qualify if:

• Aged 18 to 65 years.
• Patients with a confirmed diagnosis of Crohn's disease according to the European Crohn's and Colitis Organisation (ECCO) criteria.
• Patients with prior failure, loss of response, intolerance, or contraindication to anti-TNF therapy, who subsequently had inadequate response to ustekinumab or upadacitinib monotherapy between July 1, 2023 and May 31, 2025.
• Active Crohn's disease defined by Harvey-Bradshaw Index (HBI) \>4, or endoscopic disease activity with at least one segment having an SES-CD ulcer subscore ≥2. Postoperative endoscopic recurrence was defined as modified Rutgeerts score ≥i2b. For patients in whom the small bowel anastomosis could not be reached endoscopically, disease activity was assessed by the treating physician based on clinical symptoms, elevated inflammatory markers, and imaging findings.
• Patients who required dose reduction during full-dose upadacitinib treatment because of adverse events, or who had persistent clinical symptoms, elevated C-reactive protein, active endoscopic disease, postoperative recurrence, or active disease on imaging despite upadacitinib treatment.
• Patients with inadequate response or loss of response to ustekinumab treatment, defined by persistent clinical symptoms, elevated C-reactive protein, active endoscopic disease, postoperative recurrence, imaging evidence of active disease, or recurrence after initial response during maintenance therapy.
• Availability of inflammatory markers and imaging results within 3 months before initiation of combination therapy.

You may not qualify if:

• Patients receiving upadacitinib in combination with biologics other than ustekinumab.
• Patients receiving full-dose upadacitinib 45 mg/day in combination with ustekinumab.
• Patients with contraindications to upadacitinib, including hypersensitivity to the active substance or excipients, active tuberculosis or severe infection, malignancy, thromboembolic events, or severe hepatic impairment.
• Patients with severe infection, malignancy, pregnancy, or lactation.
• Patients with severe intestinal stricture, perforation, or intra-abdominal abscess that might require surgery and interruption of drug therapy during the study period.
• Patients considered unsuitable for the above treatment by the treating physician.
• Patients with incomplete data, inability to complete follow-up, or loss to follow-up.

Sponsors & Collaborators

• Shanghai 10th People's Hospital: lead
• Second Affiliated Hospital of Zhengzhou University: collaborator
• The First Affiliated Hospital of Anhui Medical University: collaborator

Study Sites (1)

The Tenth People's Hospital of Shanghai

Shanghai, Shanghai Municipality, 201505, China

Location

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Crohn Disease

Interventions

upadacitinib; Ustekinumab

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: July 6, 2026
• First Posted: July 13, 2026
• Study Start: July 1, 2023
• Primary Completion: December 31, 2025
• Study Completion: March 31, 2026
• Last Updated: July 13, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)