TOPLINE:

Among patients with severe ulcerative colitis (UC) who had not previously received biologic treatments, infliximab or upadacitinib produced the fastest and largest symptom improvements, both early and after the initial treatment period. Patients with severe disease were less likely to respond to certain therapies than those with moderate disease.

METHODOLOGY:

• Rapid symptom control is critical in managing UC, particularly in severe cases; although multiple advanced therapies are approved for moderate-to-severe UC, comparative data on their speed of onset of efficacy remain limited.
• Researchers conducted a post hoc analysis using individual participant-level data from 11 randomized controlled trials to compare the onset and induction efficacy of advanced therapies for UC in 1781 patients with severe endoscopic disease (Mayo endoscopic subscore [MES] 3) at baseline who were biologic-naive (mean age, 41.9 years; 41.4% women); differential responses in patients with moderate (MES 2) vs severe endoscopic disease were also explored.
• Among the included patients with severe disease, 186 received adalimumab, 81 received golimumab, 97 received infliximab, 313 received mirikizumab, 102 received ustekinumab, 245 received vedolizumab, 120 received tofacitinib, 111 received upadacitinib, and 526 received placebo; standard induction doses of therapy were administered.
• Primary outcome measure was early Patient-Reported Outcome-2 (PRO-2) response, defined as at least 50% reduction in stool frequency and rectal bleeding scores at 2-weeks from baseline.

TAKEAWAY:

• In patients with severe endoscopic disease, infliximab and upadacitinib each showed superior early efficacy, with upadacitinib demonstrating the highest odds of achieving PRO-2 response at week 2 (adjusted odds ratio [aOR], 6.38; P = .001), followed by infliximab (aOR, 4.49; P < .001).
• Among participants with moderate endoscopic disease who were biologic-naive, the highest response rates at week 2 were observed in patients receiving upadacitinib, those receiving adalimumab, and those receiving infliximab.
• In patients with severe endoscopic disease, postinduction PRO-2 response rates were highest with infliximab (aOR, 10.14; P < .001), followed by upadacitinib (aOR, 6.13; P < .001), ustekinumab (aOR, 3.16; P = .001), and mirikizumab (aOR, 1.79; P = .015).
• Patients with severe endoscopic disease showed lower odds of early and postinduction response than those with moderate disease for several therapies, including ustekinumab, tofacitinib, vedolizumab, and mirikizumab.

IN PRACTICE:

“For a patient with severe MES 3 disease, speed of onset is a priority, so it may be reasonable to prioritize use of upadacitinib or infliximab given their incremental efficacy with increasing willingness to accept higher risk profiles…. However, for a patient with MES 2 disease, agents with more favorable safety profiles such as vedolizumab, ustekinumab, or mirikizumab may be preferred due to their comparable postinduction efficacy and more favorable safety profiles,” the authors wrote.

SOURCE:

The study was led by Emily C.L. Wong, McMaster University in Hamilton, Ontario, Canada. It was published online in The American Journal of Gastroenterology.

LIMITATIONS:

Differences in study designs, induction duration, and endpoints across trials may have introduced variability in reported response rates. The generalizability to real-world settings remains uncertain because clinical trial populations often differ from routine practice. Additionally, the MES lacks granularity, and scoring of the worst lesion may have underestimated true inflammatory burden. 

DISCLOSURES:

Some authors reported receiving consulting or advisory fees, speaker or honoraria payments, research support or grants, or royalties and having other ties with various pharmaceutical companies and organizations.

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