Combined Upadacitinib and Vedolizumab as 8-Week Induction Therapy for Moderate-to-Severe Ulcerative Colitis: A...

Current advanced therapies for ulcerative colitis face an "efficacy ceiling," with endoscopic remission rates rarely exceeding 30%. We evaluated whether combination therapy-8-week induction with upadacitinib and vedolizumab followed by vedolizumab monotherapy-would be superior to standard vedolizumab monotherapy.

In this prospective, multicenter, randomized, open-label, superiority trial at 8 centers in China, adults with moderate-to-severe ulcerative colitis (modified Mayo score 4-9, endoscopic subscore ≥2) were randomized 1:2 to combination therapy (vedolizumab 300 mg intravenously at weeks 0, 2, and 6 plus upadacitinib 45 mg daily for 8 weeks) or vedolizumab monotherapy. The primary endpoint was endoscopic remission (Mayo endoscopic subscore of 0) at week 8, assessed by blinded central readers.

Of 120 randomized patients, 113 comprised the modified intention-to-treat population (40 combination, 73 monotherapy). Endoscopic remission at week 8 was achieved by 37.5% vs 15.1% (absolute risk difference, 22.4 percentage points; 95% confidence interval, 5.3-39.5; adjusted odds ratio, 3.34; 95% confidence interval, 1.34-8.58; P = .010). Clinical remission (65.0% vs 35.6%; P = .002) and histologic-endoscopic mucosal improvement (40.0% vs 13.7%; P = .004) were significantly higher with combination therapy. Adverse event rates were comparable (7.5% vs 6.8%), with no serious adverse events.

In this open-label trial, combined upadacitinib and vedolizumab induction was superior to vedolizumab monotherapy for achieving endoscopic and clinical remission at week 8 in patients with moderate-to-severe ulcerative colitis. Although these findings should be interpreted with caution, given the early trial termination and open-label design, they provide the first randomized evidence supporting a short-term combination biologic and small-molecule induction strategy.

gov, Number: NCT06095596.