Infliximab and Upadacitinib Demonstrate Superior Early Onset of Efficacy in Biologic-Naïve Ulcerative Colitis With Severe Endoscopic Disease.

Abstract

Introduction: Rapid symptom control is critical in managing ulcerative colitis (UC), especially in patients with severe disease. Although multiple advanced therapies are approved for moderate to severe UC, data comparing their speed of onset are limited. We compared the onset and induction efficacy of advanced therapies for UC among biologic-naïve patients with severe endoscopic disease (Mayo endoscopic score [MES] of 3) and explored differential responses in patients with moderate (MES 2) vs severe endoscopic disease.

Methods: This was a post hoc analysis using individual participant-level data from 11 randomized controlled trials. Biologic-naïve patients with MES 3 disease receiving standard induction regimens of infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, mirikizumab, tofacitinib, or upadacitinib were included. The primary outcome was early PRO-2 response, defined as ≥50% reduction in stool frequency and rectal bleeding scores at 2 weeks postbaseline. Secondary outcomes included postinduction clinical remission and PRO-2 remission. Logistic regression models adjusted for baseline covariates were used.

Results: A total of 1,781 biologic-naïve patients with MES 3 disease were included. Infliximab (35.1%) and upadacitinib (32.4%) demonstrated the highest early PRO-2 response rates. Compared with placebo, the highest odds of response were observed with upadacitinib (adjusted odds ratio: 6.38 [95% CI: 2.11-19.23], P = 0.001) and infliximab (adjusted odds ratio 4.49 [95% CI: 2.05-9.85], P < 0.001). At postinduction, infliximab (72.2%) and upadacitinib (59.5%) again demonstrated superior PRO-2 response rates. In comparison to MES 2 patients, those with MES 3 had reduced odds of early and postinduction response for several therapies, particularly ustekinumab, tofacitinib, vedolizumab, and mirikizumab.

Discussion: Among biologic-naïve UC patients with severe endoscopic disease, infliximab and upadacitinib had the highest rates of week 2 and postinduction PRO-2 response. Baseline disease activity may help to better inform treatment choices.