Upadacitinib plus vedolizumab inductionUC · Treatment strategy
Combined Upadacitinib and Vedolizumab as 8-Week Induction Therapy for Moderate-to-Severe Ulcerative Colitis: A Multicenter, Randomized Controlled Trial
Yao J, et al.
Clin Gastroenterol Hepatol 2026 · PMID 42173298 (PubMed, opens in a new tab) · doi 10.1016/j.cgh.2026.05.010 (full paper, opens in a new tab)
| Endpoint | Combination | Vedolizumab | Difference |
|---|---|---|---|
| Endoscopic remission, Mayo endoscopic subscore 0 (primary endpoint) | 37.5% (n=40) | 15.1% (n=73) | +22.4 points (95% CI 5.3–39.5); adjusted OR 3.34 (95% CI 1.34–8.58); P=0.010 |
| Clinical remission | 65.0% (n=40) | 35.6% (n=73) | P=0.002 |
| Histologic-endoscopic mucosal improvement | 40.0% (n=40) | 13.7% (n=73) | P=0.004 |
These are 8-week results; whether the gain lasts after upadacitinib stops is unknown.
Source: Yao 2026, abstract (modified intention-to-treat population: 40 combination, 73 monotherapy). The trial stopped early.
Structured abstract
BackgroundAdvanced therapies for UC face an efficacy ceiling, with endoscopic remission rarely above 30%. This trial tested adding 8 weeks of upadacitinib to vedolizumab induction, followed by vedolizumab alone.
MethodsProspective, multicentre (8 centres in China), randomised (1:2), open-label superiority trial with blinded central endoscopy reading; stopped early. 120 patients. Primary endpoint: Endoscopic remission (Mayo endoscopic subscore 0) at week 8, centrally read.
ResultsPrimary result. 37.5% vs 15.1%; absolute risk difference 22.4 percentage points (95% CI 5.3–39.5); adjusted odds ratio 3.34 (95% CI 1.34–8.58); P=0.010
Take-homeAdding 8 weeks of upadacitinib to vedolizumab induction improved early endoscopic remission over vedolizumab alone, but this small open-label trial is hypothesis-generating.
| Patients | 120 |
|---|---|
| Population | Adults with moderate to severe UC (modified Mayo 4–9, endoscopic subscore ≥2); 113 in the modified intention-to-treat population (40 combination, 73 monotherapy) |
| Comparison | Vedolizumab 300 mg IV at weeks 0, 2 and 6 plus upadacitinib 45 mg daily for 8 weeks vs vedolizumab alone |
| Drugs | upadacitinib, vedolizumab |
| Classes | JAK inhibitor, Anti-integrin |
| Published | Yao J, et al. Clin Gastroenterol Hepatol 2026 (published online 22 May 2026). |
Key points
- Clinical remission at week 8: 65.0% vs 35.6% (P=0.002).
- Histologic-endoscopic mucosal improvement: 40.0% vs 13.7% (P=0.004).
- Adverse events 7.5% vs 6.8%, with no serious adverse events.
- After 8 weeks, patients continued vedolizumab alone: this tests a short JAK 'bridge', not long-term dual therapy.
Limitations
- Open-label, terminated early, small, and from a single country.
- Only 8-week outcomes; durability after stopping upadacitinib is unknown.
- Combination advanced therapy is off-label.
Commentary
Context. Vedolizumab is gut-selective and safe but can be slow to act. Using a fast-acting JAK inhibitor as a short bridge is an attractive idea, and this is the first randomised evidence for it, as the authors state. It sits alongside VEGA (PMID 36738762), which combined two biologics for induction.
Use with caution. The early termination and open-label design mean the size of the benefit is uncertain. Confirmatory, blinded trials with longer follow-up are needed before this becomes routine.
Journal club
Design
Prospective, multicentre (8 centres in China), randomised (1:2), open-label superiority trial with blinded central endoscopy reading; stopped early. 120 patients.
Primary result. 37.5% vs 15.1%; absolute risk difference 22.4 percentage points (95% CI 5.3–39.5); adjusted odds ratio 3.34 (95% CI 1.34–8.58); P=0.010
Validity and applicability
- Open-label, terminated early, small, and from a single country.
- Only 8-week outcomes; durability after stopping upadacitinib is unknown.
- Combination advanced therapy is off-label.
Where it sits now
Adding 8 weeks of upadacitinib to vedolizumab induction improved early endoscopic remission over vedolizumab alone, but this small open-label trial is hypothesis-generating.
- VEGA (2023): Combining an anti-TNF with an IL-23 antibody for induction outperformed golimumab alone but did not clearly separate from guselkumab alone; this phase 2 signal needs phase 3 confirmation.
- UC-SUCCESS (2014): When starting infliximab in anti-TNF-naive UC, adding azathioprine improves steroid-free remission at 16 weeks (40% vs 22%).
Questions for discussion
- Outcomes were measured at week 8, when upadacitinib stopped. What would you need to know about week 52 before adopting this strategy?
- The trial was open-label, but endoscopy was centrally read. Which endpoints are most and least vulnerable to bias?
- Would you use a short JAK bridge with vedolizumab in a patient at high thrombotic risk? What alternatives are there?