Upadacitinib/Vedolizumab Induction in Moderate-to-Severe UC

August 11, 2026

Issue 15

Clinical Question

Is upadacitinib/vedolizumab induction superior to vedolizumab monotherapy in moderate-to-severe UC?

Editor’s Bottom Line

These results show a substantial gain in efficacy with no apparent compromise in safety through combining two advanced therapies for ulcerative colitis. Long-term data are needed to ensure both safety and efficacy are sustained.

Reference

Yao J, Wu H, Wu L, et al. Combined Upadacitinib and Vedolizumab as 8-Week Induction Therapy for Moderate-to-Severe Ulcerative Colitis: A Multicenter, Randomized Controlled Trial. Clin Gastroenterol Hepatol. Epub ahead of print May 21, 2026. https://doi.org/10.1016/j.cgh.2026.05.010

Synopsis

This prospective, multicenter, open-label, superiority randomized controlled trial, conducted at eight centers in China, enrolled adults aged 18 to 60 years with moderately to severely active UC, defined as a modified Mayo score 4–9 with endoscopic subscore ≥2. Patients were randomized 1:2 to combination induction with vedolizumab 300 mg IV at weeks 0, 2, and 6 plus upadacitinib 45 mg daily for 8 weeks, or monotherapy with 300 mg IV vedolizumab at weeks 0, 2, and 6. The primary endpoint was endoscopic remission (Mayo endoscopic subscore of 0) at week 8, assessed by blinded central readers. Enrollment was stopped early after the primary endpoint was met at a planned interim analysis, with 113 of 334 planned patients enrolled.

The modified intention-to-treat (mITT) population comprised 40 combination and 73 monotherapy patients. The cohort was predominantly corticosteroid-naïve (73%) but endoscopically severe (61% with subscore 3), with approximately 12% having failed prior tumor necrosis factor (TNF) therapy. Endoscopic remission at week 8 was achieved by 37.5% of the combination group vs. 15.1% of the monotherapy group (absolute risk difference: 22.4 percentage points; 95% Confidence Interval [CI], 5.3-39.5; adjusted Odds Ratio [aOR]: 3.34; 95% CI, 1.34–8.58; p=0.010).

Clinical remission (65% vs. 35.6%; aOR: 3.68; p=0.002) and histologic-endoscopic mucosal improvement (HEMI; 40% vs. 13.7%; aOR: 3.97; p=0.004) were also significantly higher with combination therapy. No significant differences were observed in rates of clinical response, deep mucosal healing or patient-reported quality of life. A significant interaction was detected between combination therapy and prior TNF antagonist exposure for clinical remission (P for interaction = 0.040), with the clinical remission benefit more pronounced in TNF-naïve patients (aOR: 4.48; 95% CI, 1.82–11.85) than in those with prior TNF antagonist exposure. This interaction was not observed for the primary endoscopic remission endpoint.

Adverse event rates were low and comparable between groups (7.5% vs. 6.8%), with no serious adverse events, herpes zoster infections or thromboembolic events in either group during the 8-week induction period. One patient in the combination group discontinued due to severe rash and hyperlipidemia.

Details

Study Design: Prospective multicenter open-label randomized controlled superiority trial
Funding: National Natural Science Foundation of China, Sun Yat-sen University, Guangdong Provincial Clinical Research Center for Digestive Diseases and China Health Promotion Foundation
Allocation: Randomized (1:2)
Setting: Multicenter
Level of Evidence: 1b