Infliximab and Upadacitinib Show Earlier Onset of Efficacy for Severe Ulcerative Colitis

IBD

Bincy P. Abraham, MD, MS reviewing Wong ECL, et al. Am J Gastroenterol 2026 Feb 2.

In patients with severe ulcerative colitis, clinical symptoms can contribute to a significantly worse quality of life, sometimes requiring hospitalization. Rapid-onset medical therapy is necessary to improve symptoms and, ideally, prevent hospitalizations, or, among hospitalized patients, to facilitate discharge or early identification of those who require surgery.

In this analysis of 11 randomized controlled trials including 1781 biologic-naïve patients with severe endoscopic disease (Mayo endoscopic subscore [MES] of 3), infliximab (35.1%) and upadacitinib (32.4%) demonstrated the fastest onset of symptomatic improvement. By week 2, both agents delivered markedly higher PRO‑2 (patient-reported outcome) response rates than placebo, with upadacitinib showing the greatest adjusted odds of early response, followed closely by infliximab. Other advanced therapies, including ustekinumab, mirikizumab, vedolizumab, and tofacitinib, were effective but exhibited slower early symptom resolution, highlighting significant heterogeneity in onset of action across agents with different mechanisms of action. By postinduction, all advanced therapies showed clinically meaningful efficacy, but infliximab and upadacitinib maintained the highest PRO‑2 response rates.

Comment:

Clinically, this comparative evidence underscores the importance of endoscopic severity as a treatment‑selection variable. For patients presenting with severe MES 3 inflammation requiring rapid clinical improvement, infliximab or upadacitinib can provide the most reliable early relief. For those with moderate disease (MES 2), therapies with favorable safety profiles, such as vedolizumab, ustekinumab, and mirikizumab, remain strong induction options given their comparable postinduction outcomes. These findings support individualizing ulcerative colitis induction therapy based on endoscopic severity and the medication’s mechanism of action.

Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.

Bincy P. Abraham, MD, MS

Bio and Disclosures

Citation(s):

Wong ECL, Jairath V, Dulai PS, et al. Infliximab and upadacitinib demonstrate superior early onset of efficacy in biologic-naïve ulcerative colitis with severe endoscopic disease. Am J Gastroenterol 2026 Feb 2. (Epub ahead of print) (https://doi.org/10.14309/ajg.0000000000003940)