Real-World Effectiveness and Safety of Upadacitinib Plus Vedolizumab vs Upadacitinib Monotherapy During Induction in Moderate-to-Severe Ulcerative Colitis

Official title

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

Overview

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.

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.

Interventions

• Drug Upadacitinib
  Oral Upadacitinib 45mg/d for 8 weeks in the induction therapy.
• Drug Vedolizumab
  Vedolizumab 300mg intravenously on weeks 0, 2, 6.

Primary outcome measures

• Clinical remission rate at the 8th-week [Time frame: 8th-week]

Secondary outcome measures (3)

• Clincial response rate at the 8th week [Time frame: 8th-week]
• C-Reactive Protein normalization rate at the 8th week [Time frame: 8th-week]
• Endoscopic remission rate at the 8th week [Time frame: 8th-week]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 6 centers

• The First People's Hospital of Foshan — Foshan
• Foshan Fosun Chancheng Hospital, Foshan — Foshan
• The Sixth Affiliated Hospital, South China University of Technology City: Foshan — Foshan
• the Sixth Affiliated Hospital of Sun Yat-sen University — Guangzhou
• The Second Affiliated Hospital of Guangzhou Medical University — Guangzhou
• the Second Affiliated Hospital of Shenzhen University (People's Hospital of Shenzhen Bao'a — Shenzhen

Publications

• 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 a PMID 42173298
• 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. PMID 40490017
• 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, PMID 35644166

Identifiers

NCT: NCT07442045 · 2026ZSLYEC-079

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗