Crohn's Disease, Inflammatory Bowel Disease (IBD)
Conditions
Keywords
Ustekinumab, Upadacitinib, refractory Crohn's disease
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.
Detailed description
This is a multicenter, retrospective, real-world observational study conducted at several inflammatory bowel disease centers in China. The study is designed to evaluate the effectiveness and safety of ustekinumab (UST) combined with low-dose upadacitinib (UPA; 15 mg/day or 30 mg/day) in patients with moderate-to-severe active refractory Crohn's disease. Eligible patients received combination therapy between July 1, 2023 and December 31, 2025. Patients were required to have previously failed, been intolerant to, or experienced adverse events with anti-tumor necrosis factor therapy, followed by an inadequate response or intolerance to UST monotherapy or UPA 45 mg/day administered for 12 weeks. The combination regimen consisted of intravenous re-induction with UST and oral low-dose UPA at 15 mg/day or 30 mg/day for 12 weeks. Clinical response and clinical remission are assessed at weeks 12 to 16, while endoscopic response and endoscopic remission are assessed between weeks 12 and 24. Maintenance treatment after the initial 12-week combination period and safety outcomes through week 24 are also evaluated. Data are obtained retrospectively from existing medical records, and no study-specific intervention is assigned to participants.
Interventions
DRUGUpadacitinib
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.
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.
Sponsors
Shanghai 10th People's Hospital
The First Affiliated Hospital of Anhui Medical University
Second Affiliated Hospital of Zhengzhou University
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical remission rate at Week 12 to Week 16 | Week 12 to Week 16 after initiation of combination therapy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Endoscopic healing rate at Week 12 to Week 24 | Week 12 to Week 24 after initiation of combination therapy | The proportion of patients achieving endoscopic healing at Week 12 to Week 24 after initiation of combination therapy. Endoscopic healing is defined as SES-CD ≤2, or modified Rutgeerts score \<i2b in postoperative patients. |
| Endoscopic response rate at Week 12 to Week 24 | Week 12 to Week 24 after initiation of combination therapy | The proportion of patients achieving endoscopic response at Week 12 to Week 24. Endoscopic response is defined as a \>50% decrease in SES-CD from baseline, a decrease of ≥2 points from baseline in patients with a baseline SES-CD of 4, or a decrease of ≥1 point in the modified Rutgeerts score. |
Countries
China
Outcome results
None listed