Upadacitinib Plus Vedolizumab Induction in Moderate-To-Severe UC

Key Takeaways

• Endoscopic remission was observed more often with combination induction than with vedolizumab alone at the week-8 assessment.
• Combination therapy also showed higher clinical remission and histologic-endoscopic mucosal improvement at week 8.
• Adverse-event rates were similar, no serious adverse events were reported, and the findings warrant caution because of early termination and the open-label design.

Week-8 endoscopic remission was higher with upadacitinib plus vedolizumab than with vedolizumab alone in adults with moderate-to-severe ulcerative colitis, at 37.5% versus 15.1%. Researchers tested this 8-week induction approach in China in a multicenter randomized trial. The study compared short-term combination induction with vedolizumab monotherapy in a head-to-head design, with outcomes assessed through week 8.

This prospective, multicenter, randomized, open-label superiority trial was conducted at 8 centers in China in adults with moderate-to-severe ulcerative colitis. Eligibility required a modified Mayo score of 4-9 and an endoscopic subscore of at least 2. Participants were randomized 1:2 to vedolizumab 300 mg intravenously at weeks 0, 2, and 6 plus upadacitinib 45 mg daily for 8 weeks, or to vedolizumab monotherapy. After the 8-week combination induction period, treatment continued with vedolizumab monotherapy. The prespecified primary endpoint was week-8 endoscopic remission, defined as a Mayo endoscopic subscore of 0 and assessed by blinded central readers.

Among 120 randomized patients, 113 comprised the modified intention-to-treat population, including 40 in the combination group and 73 in the monotherapy group. Endoscopic remission at week 8 occurred in 37.5% versus 15.1%, for an absolute risk difference of 22.4 percentage points with a 95% CI of 5.3-39.5. The adjusted odds ratio was 3.34 with a 95% CI of 1.34-8.58, and P = .010. The week-8 primary endpoint favored the combination regimen.

Secondary efficacy outcomes also favored the combination arm at week 8. Clinical remission was 65.0% versus 35.6%, with P = .002, and histologic-endoscopic mucosal improvement was 40.0% versus 13.7%, with P = .004. Short-term adverse-event rates were 7.5% versus 6.8%, and no serious adverse events were reported. The week-8 safety summary was similar between groups.

The investigators said these findings should be interpreted cautiously because the trial ended early and used an open-label design. They described the study as the first randomized evidence supporting a short-term combination biologic and small-molecule induction strategy.