TOPLINE:

In adults with moderate-to-severe ulcerative colitis (UC), an 8-week induction with upadacitinib plus vedolizumab increased the rate of endoscopic remission by more than twofold at week 8 and improved clinical and histologic outcomes compared with vedolizumab alone, all while showing a comparable short-term safety profile with no new serious safety signals.

METHODOLOGY:

• The endoscopic remission rates of current advanced therapies for UC have rarely exceeded 30%; hence, researchers evaluated whether an 8-week induction of upadacitinib plus vedolizumab followed by vedolizumab maintenance was superior to vedolizumab monotherapy.
• They conducted an open-label superiority trial at eight centers in China, enrolling 120 patients with moderate-to-severe UC (modified Mayo score, 4-9; endoscopic subscore ≥ 2). Patients were randomly assigned to receive combination therapy (vedolizumab 300 mg intravenously at weeks 0, 2, and 6 plus upadacitinib 45 mg daily for 8 weeks) or vedolizumab monotherapy.
• The final analysis was conducted in 113 patients (mean age, 42 years; 70% male) who received at least one dose of study medication; 40 vs 73 patients were included in the combination therapy group vs the monotherapy group.
• The primary endpoint was the achievement of endoscopic remission (Mayo endoscopic subscore, 0) at week 8. Secondary endpoints included clinical remission, clinical response, endoscopic improvement, histologic-endoscopic mucosal improvement, and deep mucosal healing at week 8.

TAKEAWAY:

• Endoscopic remission at week 8 was achieved by 37.5% vs 15.1% of patients in the combination therapy group vs the monotherapy group (absolute risk difference, 22.4 percentage points; 95% CI, 5.3-39.5; adjusted odds ratio [OR], 3.34; P = .010).
• Clinical remission rates were significantly higher with combination therapy than with monotherapy (65.0% vs 35.6%; adjusted OR, 3.68; P = .002), as were histologic-endoscopic mucosal improvement rates (40.0% vs 13.7%; adjusted OR, 3.97; P = .004).
• Endoscopic improvement was also significantly greater in the combination therapy group than in the monotherapy group (P = .035); however, no significant differences were observed between the groups for clinical response, endoscopic response, or deep mucosal healing.
• During the 8-week induction, adverse events were infrequent and similar between the groups; no serious adverse events were reported.

IN PRACTICE:

“These findings provide initial randomized evidence for a combination biologic and small-molecule induction strategy,” the authors of the study wrote.

SOURCE:

The study was led by Jiayin Yao, Hongzhen Wu, and Luying Wu, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. It was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS:

The open-label design may have been a potential source of bias. The trial was stopped early after enrolling approximately one third of the planned sample. Fecal calprotectin was not collected as part of the study protocol.

DISCLOSURES:

The study received funding from the National Natural Science Foundation of China, Project 5010 of Sun Yat-Sen University, and other sources. All authors reported having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.