TOPLINE

A multicenter real-world study of patients with refractory moderate-to-severe ulcerative colitis (UC) showed that upadacitinib outperformed tofacitinib and ustekinumab — advanced treatment options recommended for UC after failure of prior treatment — with greater effectiveness at both 16 and 52 weeks of follow-up.

METHODOLOGY

• Despite guidelines naming upadacitinib, tofacitinib, and ustekinumab as high-efficacy second-line options for UC after treatment failure, real-world head-to-head studies comparing the three drugs have been scarce.
• Researchers conducted a retrospective, multicenter cohort study across nine Portuguese hospitals, enrolling 312 adults (57.1% women; mean age at diagnosis, 32.6 years) with refractory moderate-to-severe UC who had not responded to at least one prior advanced therapy.
• Patients initiated treatment with upadacitinib (n = 103), tofacitinib (n = 74), or ustekinumab (n = 135).
• The primary outcome was steroid-free clinical remission, characterized by no clinical symptoms and no corticosteroid use for at least 30 days at 16 weeks or 90 days at 52 weeks; secondary outcomes were biochemical remission (fecal calprotectin level ≤ 250 µg/g) and endoscopic remission (Mayo endoscopic subscore of 0); outcomes were assessed at 16 and 52 weeks.
• A subanalysis assessed the same outcomes at 16 weeks among the subset of patients (n = 146) who received each drug specifically as second-line therapy.

TAKEAWAY

• Steroid-free clinical remission was consistently higher with upadacitinib than with tofacitinib or ustekinumab — 47.6% with upadacitinib vs 27.0% with tofacitinib and 26.7% with ustekinumab at 16 weeks and 75.0% with upadacitinib vs 52.4% with tofacitinib and 53.4% with ustekinumab at 52 weeks; at both timepoints, upadacitinib was associated with significantly higher odds of steroid-free clinical remission than tofacitinib (odds ratio [OR], 2.56 at 16 weeks and 3.14 at 52 weeks) or ustekinumab (OR, 3.71 at 16 weeks and 4.68 at 52 weeks).
• For biochemical remission at 16 weeks, upadacitinib outperformed tofacitinib (OR, 3.44) and ustekinumab (OR, 3.73); at week 52, upadacitinib showed higher odds of biochemical remission than ustekinumab (OR, 4.14). Upadacitinib also demonstrated superior endoscopic remission at 16 weeks compared with tofacitinib (OR, 7.44) and ustekinumab (OR, 3.34), with this advantage sustained at 52 weeks.
• A subanalysis restricted to patients receiving each drug as their second-line therapy (n = 146) confirmed the same pattern, with upadacitinib showing higher odds of steroid-free remission than tofacitinib (OR, 6.30) and ustekinumab (OR, 3.04).
• In terms of safety, all three drugs performed well, with no meaningful differences in serious adverse events between the groups.

IN PRACTICE

"Despite the superior performance of upadacitinib, all therapies were effective in refractory UC, even using the strict remission criteria applied in this study," the authors wrote.

"Other factors — such as greater symptom burden, higher calprotectin levels, and higher endoscopic inflammatory activity — may influence treatment response and have been associated with an increased risk of relapse," they added.

SOURCE

The study was led by Joana Camões Neves and Dalila Costa of the Gastroenterology Department, Unidade Local de Saúde Braga, Braga, Portugal. It was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS

This study was retrospective, and some data were missing. Although the analysis tried to make the treatment groups more comparable, differences between the groups may still have affected the results. In addition, upadacitinib was used later during the study period, and follow-up data were less complete at 52 weeks, which may have affected the reliability of the subsequent findings.

DISCLOSURES

The study did not receive any external funding. The authors reported having no relevant financial, professional, or personal 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.