Real-World Effectiveness and Safety of Upadacitinib Plus Vedolizumab vs Upadacitinib Monotherapy During Induction in Moderate-to-Severe Ulcerative Colitis
Real-World Comparative Effectiveness and Safety of Upadacitinib Plus Vedolizumab Versus Upadacitinib Monotherapy During Induction in Moderate-to-Severe Ulcerative Colitis: A Multicenter Retrospective Cohort Study
This multicenter retrospective comparative cohort study evaluated the real-world effectiveness and safety of upadacitinib plus vedolizumab compared with upadacitinib monotherapy during 8-week induction in adults with moderate-to-severe ulcerative colitis.
Consecutive eligible patients who initiated upadacitinib induction therapy, either as monotherapy or with concomitant vedolizumab, between January 2023 and September 2025 at six tertiary inflammatory bowel disease referral centers in China were included.
The primary outcome was modified Mayo clinical remission at week 8. Secondary outcomes were modified Mayo clinical response, C-reactive protein normalization among patients with an elevated baseline C-reactive protein concentration, and endoscopic remission. Safety outcomes were assessed from the index date through the week-8 assessment.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This multicenter retrospective comparative cohort study was conducted at six tertiary inflammatory bowel disease referral centers in China. Consecutive adults with moderate-to-severe ulcerative colitis who initiated upadacitinib induction therapy, either as monotherapy or with concomitant vedolizumab, between January 2023 and September 2025 were screened for eligibility.
The index date was defined as the date of upadacitinib initiation. Treatment exposure was classified according to the regimen initiated at the index date: upadacitinib monotherapy or upadacitinib plus vedolizumab. The same eligibility criteria, treatment exposure definitions, assessment windows, outcome definitions, and statistical procedures were applied to both treatment groups.
Patients in the combination-therapy group received oral upadacitinib 45 mg once daily for 8 weeks and intravenous vedolizumab 300 mg at weeks 0, 2, and 6. Patients in the monotherapy group received oral upadacitinib 45 mg once daily for 8 weeks without concomitant vedolizumab or another advanced therapy.
Baseline clinical and biochemical assessments were defined as the most recent eligible assessments obtained before or on the index date. Week-8 clinical, biochemical, and endoscopic assessments were defined as the eligible assessments closest to day 56 after upadacitinib initiation. Endoscopic recordings were centrally reviewed by blinded gastroenterologists, and disagreements were resolved by a third blinded adjudicator.
The primary outcome was modified Mayo clinical remission at week 8. Secondary outcomes were modified Mayo clinical response, C-reactive protein normalization among patients with an elevated baseline C-reactive protein concentration, and endoscopic remission. Safety was assessed from the index date through the week-8 assessment.
The primary analysis used propensity score-based stabilized inverse probability of treatment weighting, targeting the average treatment effect in the study population. Adjusted risk differences were estimated using survey-weighted linear probability models, and adjusted risk ratios were estimated using survey-weighted quasi-Poisson regression models with robust design-based standard errors. Sensitivity analyses included stabilized weights truncated at the 1st and 99th percentiles, overlap weighting, and conventional multivariable logistic regression without propensity-score weighting.
The protocol was reviewed and approved by the Research Ethics Committee of The Sixth Affiliated Hospital, Sun Yat-sen University (approval number 2026ZSLYEC-079). The requirement for informed consent was waived because the study involved retrospective analysis of de-identified clinical data.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Jiayin Yao
- Phone Number: 13826462890
- Email: yjyin@mail2.sysu.edu.cn
Study Locations
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Guangdong
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Foshan, Guangdong, China, 510260
- Recruiting
- The first people's Hospital of Foshan
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Contact:
- Peizhu Su, MD
- Email: supeizhu1986@163.com
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Foshan, Guangdong, China, 528000
- Recruiting
- Foshan Fosun Chancheng Hospital, Foshan
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Contact:
- Ji Wu, MD
- Email: 13929190198@139.com
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Foshan, Guangdong, China, 528200
- Recruiting
- The Sixth Affiliated Hospital, South China University of Technology City: Foshan
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Contact:
- Huangwei Chen, MD
- Email: chw1364@163.com
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Guangzhou, Guangdong, China, 510260
- Recruiting
- The Second Affiliated Hospital of Guangzhou Medical University
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Contact:
- Tingting Xie, MD
- Email: jianning.22@163.com
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Guangzhou, Guangdong, China, 501655
- Recruiting
- The Sixth Affiliated Hospital of Sun yat-sen University
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Contact:
- Jiayin Yao, MD
- Email: yjyin@mail2.sysu.edu.cn
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Shenzhen, Guangdong, China, 518000
- Recruiting
- the Second Affiliated Hospital of Shenzhen University (People's Hospital of Shenzhen Bao'an District)
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Contact:
- Xiaoyu Liu, MD
- Email: LXY-631@126.com
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
The study population consisted of consecutive adults aged 18 years or older with an established diagnosis of moderate-to-severe ulcerative colitis who initiated upadacitinib induction therapy, either as monotherapy or with concomitant vedolizumab, at six tertiary inflammatory bowel disease referral centers in China between January 2023 and September 2025.
The index date was defined as the date of upadacitinib initiation. Treatment was selected by the treating physician as part of routine clinical care.
Description
Inclusion Criteria:
- Age 18 years or older at the index date.
- Established diagnosis of ulcerative colitis for at least 3 months, supported by compatible clinical, endoscopic, and histologic findings.
- Moderately to severely active ulcerative colitis at baseline, defined as a modified Mayo score of 4 to 9 and a Mayo endoscopic subscore of at least 2.
- Initiation of upadacitinib induction therapy during the predefined study period.
- For the combination-therapy group, initiation of vedolizumab concomitantly with upadacitinib at the index date.
Exclusion Criteria:
- Crohn's disease, inflammatory bowel disease unclassified, indeterminate colitis, or another form of non-ulcerative-colitis colitis.
- Previous colectomy or colectomy planned at the index date.
- Previous exposure to upadacitinib or vedolizumab.
- Initiation of another biologic or small-molecule advanced therapy during the 8-week induction period, except for vedolizumab in the combination-therapy group.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
Upadacitinib Plus Vedolizumab
Patients received oral upadacitinib 45 mg once daily for 8 weeks and intravenous vedolizumab 300 mg at weeks 0, 2, and 6 during induction.
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Oral Upadacitinib 45mg/d for 8 weeks in the induction therapy.
Vedolizumab 300mg intravenously on weeks 0, 2, 6.
|
|
Upadacitinib Monotherapy
Patients received oral upadacitinib 45 mg once daily for 8 weeks without concomitant vedolizumab or another advanced therapy.
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Oral Upadacitinib 45mg/d for 8 weeks in the induction therapy.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Clinical remission rate at the 8th-week
Time Frame: 8th-week
|
Clinical remission is defined as a total Mayo score ≤2, with no individual subscore >1 and a rectal bleeding subscore of 0.
|
8th-week
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Endoscopic remission rate at the 8th week
Time Frame: 8th-week
|
Endoscopic remission is defined as Mayo endoscopic score(MES) =0
|
8th-week
|
|
Clincial response rate at the 8th week
Time Frame: 8th-week
|
Clinical response was defined as a decrease from baseline in the modified Mayo score of at least 2 points and at least 30%, accompanied by either a decrease in the rectal-bleeding subscore of at least 1 point or an absolute rectal-bleeding subscore of 1 or less.
|
8th-week
|
|
C-Reactive Protein normalization rate at the 8th week
Time Frame: 8th-week
|
C-reactive protein normalization was evaluated only among patients with a baseline C-reactive protein concentration greater than 5 mg/L.
Normalization was defined as a week-8 serum C-reactive protein concentration of 5 mg/L or less.
Patients with a baseline C-reactive protein concentration of 5 mg/L or less were not included in the denominator for this outcome.
|
8th-week
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Adverse Events During the 8-Week Induction Period
Time Frame: Week 0 to Week 8
|
Safety outcomes included any adverse event, serious adverse events, and permanent treatment discontinuation due to an adverse event.
Infections, herpes zoster, thromboembolic events, cardiovascular events, and clinically relevant laboratory abnormalities were recorded when explicitly documented in the electronic medical records, laboratory systems, or medication-administration records.
|
Week 0 to Week 8
|
Collaborators and Investigators
Publications and helpful links
General Publications
- Danese S, Vermeire S, Zhou W, Pangan AL, Siffledeen J, Greenbloom S, Hebuterne X, D'Haens G, Nakase H, Panes J, Higgins PDR, Juillerat P, Lindsay JO, Loftus EV Jr, Sandborn WJ, Reinisch W, Chen MH, Sanchez Gonzalez Y, Huang B, Xie W, Liu J, Weinreich MA, Panaccione R. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. Lancet. 2022 Jun 4;399(10341):2113-2128. doi: 10.1016/S0140-6736(22)00581-5. Epub 2022 May 26.
- Yao J, Wu H, Wu L, Yu Q, Cao X, Xie T, Zhong X, Chen H, Wu J, Liu X, Shi L, Zhang M, Peng X, Deng J, Wang W, Liu T, Su T, Yang H, Xia D, Zhi M. Combined Upadacitinib and Vedolizumab as 8-Week Induction Therapy for Moderate-to-Severe Ulcerative Colitis: A Multicenter, Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2026 May 22:S1542-3565(26)00388-5. doi: 10.1016/j.cgh.2026.05.010. Online ahead of print.
- Gilmore R, Murali A, Etchegaray A, Swe E, An YK, Begun J. Upadacitinib and vedolizumab combination therapy for the management of refractory ulcerative colitis and Crohn's disease. Intest Res. 2025 Oct;23(4):475-482. doi: 10.5217/ir.2024.00174. Epub 2025 Jun 9.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2026ZSLYEC-079
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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