NCT07442045

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

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 150 (estimated)
• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This multicenter retrospective cohort study evaluates the real-world effectiveness and safety of upadacitinib used alone or in combination with vedolizumab in adult patients with moderate-to-severe ulcerative colitis (UC). UC is a chronic inflammatory bowel disease that often requires long-term management, and monotherapy may reach a therapeutic ceiling in clinical practice. Combination therapy with upadacitinib, a rapid-acting oral JAK inhibitor, and vedolizumab, a gut-selective biologic, may provide complementary benefits. The study uses existing clinical and laboratory data from six Chinese IBD centers to compare short-term outcomes, including clinical remission, clinical response, endoscopic remission, normalization of C-reactive protein, and occurrence of adverse events during the 8-week induction period. This study reflects routine clinical practice and aims to provide real-world evidence to support treatment decisions in patients with moderate-to-severe UC.

Detailed description

This multicenter retrospective cohort study aims to compare the real-world effectiveness and safety of upadacitinib in combination with vedolizumab versus upadacitinib monotherapy in adult patients with moderate-to-severe ulcerative colitis (UC). Ulcerative colitis is a chronic relapsing inflammatory bowel disease requiring long-term management. Although multiple biologic agents and small-molecule therapies have been approved, the efficacy of monotherapy in moderate-to-severe disease remain limited. Increasing evidence suggests that combination strategies using two targeted therapies may overcome the therapeutic ceiling observed with single-agent treatment. Upadacitinib, an oral selective Janus kinase (JAK) inhibitor, is characterized by rapid onset of action, while vedolizumab, a gut-selective anti-integrin biologic, has a favorable safety profile but relatively slower onset. The combination of these agents may theoretically provide complementary mechanisms, enabling rapid induction of remission together with sustained disease control. However, direct comparative real-world evidence evaluating these two treatment strategies remains limited. This study is conducted in routine clinical practice settings across six tertiary inflammatory bowel disease centers in China. Patients were identified through institutional pharmacy databases and electronic medical records. The study period includes patients treated between January 2023 and December 2025. The index date was defined as the initiation of upadacitinib therapy. Patients were categorized according to baseline treatment strategy into two groups: upadacitinib monotherapy or upadacitinib in combination with vedolizumab .Eligible patients were adults (≥18 years) with moderate-to-severe UC, defined as a baseline modified Mayo score ≥4 and an endoscopic subscore ≥2. Baseline demographic and clinical variables included age, sex, smoking history, disease extent, disease duration, prior exposure to corticosteroids, exclusive enteral nutrition, immunosuppressants, and infliximab. Laboratory parameters collected at baseline and at week 8 included C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin, hemoglobin, and platelet count. Endoscopic Mayo score and modified Mayo score were also assessed at baseline and week 8. The primary outcome was clinical remission at week 8. Secondary outcomes included clinical response at week 8, endoscopic remission at week 8, CRP normalization at week 8, and occurrence of adverse events during the 8-week induction period. Baseline characteristics were summarized descriptively. Multivariable regression models and propensity score matching methods were applied to adjust for potential confounding factors and baseline imbalances between treatment groups. Sensitivity analyses were conducted to assess the robustness of findings. This study was conducted in routine clinical practice settings and was approved by the institutional review boards of all participating centers.

Conditions

• Ulcerative Colitis (UC)

Interventions

Type	Name	Description
DRUG	Upadacitinib	Oral Upadacitinib 45mg/d for 8 weeks in the induction therapy.
DRUG	Vedolizumab	Vedolizumab 300mg intravenously on weeks 1, 2, 6.

Timeline

• Start date: 2023-01-01
• Primary completion: 2025-09-30
• Completion: 2026-06-01
• First posted: 2026-03-02
• Last updated: 2026-03-02

Locations

1 site across 1 country: China