TOPLINE

In biologic-naive patients with moderate-to-severe ulcerative colitis, upadacitinib and infliximab demonstrated rapid onset of efficacy, with the administration of upadacitinib tied to higher odds of achieving a Patient-Reported Outcome (PRO)-2 response as early as week 2 and upadacitinib showing postinduction efficacy comparable to infliximab.

METHODOLOGY

• Treatment of ulcerative colitis includes multiple drug classes (eg, TNF antagonists, JAK inhibitors, anti-integrins, sphingosine-1-phosphate receptor modulators, and interleukin-12/23 inhibitors), but differences in trial endpoints and assessment timeframes make it difficult to compare how quickly they work, leaving a key gap in clinical decision-making when rapid relief from symptoms is needed.
• Researchers conducted a post hoc analysis using individual participant-level data from several phase 3 and 4 randomized controlled trials to compare the speed of onset and induction efficacy of advanced therapies in biologic-naive patients with moderate-to-severe ulcerative colitis.
• A total of 3573 biologic-naive patients (mean age across groups, 40.8 years; 59.2% women) who received adalimumab (n = 338), golimumab (n = 149), infliximab (n = 241), mirikizumab (n = 542), tofacitinib (n = 193), upadacitinib (n = 300), ustekinumab (n = 156), vedolizumab (n = 431), or placebo (n = 1223) were included.
• Participants had moderate or severe endoscopic disease at baseline (Mayo endoscopic score of 2 or 3) and received standard induction doses of therapy; infliximab was used as the comparator for all analyses.
• The primary endpoint was achieving a PRO-2 response at week 2, defined as a minimum 50% improvement in patient-reported rectal bleeding and stool frequency (SF) scores; secondary outcomes were achieving a PRO-2 response post-induction as well as achieving PRO-2 remission at week 2 and post-induction (defined as having an SF score ≤ 1 and a rectal bleeding subscore of 0).

TAKEAWAY

• At week 2, patients who received upadacitinib achieved the highest PRO-2 response rate at 65%, followed by those on infliximab (36.5%), vedolizumab (31.1%), adalimumab (30.2%), tofacitinib (30.1%), golimumab (29.5%), ustekinumab (26.9%), and mirikizumab (24.9%).
• At week 2, patients who received upadacitinib had significantly higher odds of achieving early PRO-2 response than those who received infliximab (adjusted odds ratio [aOR], 3.57), whereas the administration of mirikizumab (aOR, 0.46), ustekinumab (aOR, 0.60), and adalimumab (aOR, 0.67) was associated with significantly lower odds of achieving a response (P < .05 for all).
• Postinduction, upadacitinib was the only therapy with a PRO-2 response comparable to infliximab, and most other therapies were associated with significantly lower odds of achieving a response (P < .001 for all).
• At week 8, the administration of adalimumab, golimumab, and upadacitinib was associated with lower odds of postinduction PRO-2 remission than the administration of infliximab (P ≤ .001 for all), whereas the administration of mirikizumab, ustekinumab, vedolizumab, and tofacitinib showed no significant differences.

IN PRACTICE

“The rapid symptom control provided by upadacitinib and infliximab may be particularly advantageous for patients with a high symptom burden where quick improvement is the priority, particularly in those who are at risk of hospitalization or for those who may not tolerate concurrent steroid induction. Conversely, for patients where immediate rescue is less critical, the slightly slower onset of agents like vedolizumab, ustekinumab, and mirikizumab should be considered, given their potentially favorable safety profiles and targeted mechanisms of action,” the authors of the study wrote.

“Clinicians should view these agents as a spectrum of options, where the need for speed of onset is balanced against long-term safety and patient preference,” they added.

SOURCE

The study was led by Emily C.L. Wong, Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University in Hamilton, Ontario, Canada. It was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS

The underlying trials varied in design, induction duration, and the precise timing of assessments. Despite adjustments, residual confounding may have remained. The stringent inclusion criteria of clinical trials may have limited the generalizability of the findings.

DISCLOSURES

No funding information was mentioned for the study. Some authors disclosed receiving honoraria, research support, royalties, and consulting and/or speaker fees and serving on advisory boards for industry.

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