G Privitera et al. Clin Gastroenterol Hepatl 2026; 24: 2539-2550. Open Access! Ustekinumab and Janus Kinase Inhibitors Outperform Vedolizumab as Second-Line Therapy in Anti-Tumor Necrosis Factor-Experienced Patients With Ulcerative Colitis

Before reading this article, I had to research why it was called “The Podium Study.” The research directly stacks three competing second-line classes of advanced therapies against each other: vedolizumab, ustekinumab, and JAK inhibitors; this is similar to a sports podium (1st, 2nd, and 3rd place), as the ultimate clinical goal of the study was to “rank” which medication performed best in terms of efficacy and safety after a patient fails anti-TNFα therapy. Of historical interest, there was an older, unrelated PODIUM trial, which stood for Pentasa Once Daily in Ulcerative Colitis for Maintenance of Remission.

Methods: In this retrospective, multicenter European study, there were 596 patients were included (301 vedolizumab, 149 ustekinumab, 146 JAKi) with a mean age of 43.9 ± 15.5 years.  JAKi included 114 with tofacitinib, 28 with upadacitinib, and 5 with filgotinib. Achievement of biochemical steroid-free clinical remission (SFCR) within 12 months was identified by having SFCR associated with biomarker normalization: FCP <250 μg/g or CRP <5 mg/L—if discordant, FCP was considered the reference biomarker.

Key findings:

• Compared with vedolizumab, both ustekinumab and JAKi showed significantly higher probability of steroid-free clinical remission (SFCR) (aHR, 1.54 and aHR, 1.66, respectively) and biochemical SFCR (aHR, 2.26 and 3.37, respectively) at 12 months
• The crude incidence rate of SFCR at 12 months was 65.3% for vedolizumab, 87.0% for ustekinumab, and 80.2% for JAKi.
• From a safety standpoint, JAKi were associated with an approximately 4-fold increase in the incidence rate of treatment-related AEs—primarily infections—compared with both vedolizumab and ustekinumab.

Discussion Points:

“Optimal sequencing in UC after anti-TNF-α exposure remains an open issue, as direct comparisons are scarce. Overall, our findings are consistent with the network meta-analysis by Lasa et al, which reported superior efficacy of JAKi and ustekinumab compared with vedolizumab in inducing clinical remission and endoscopic improvement in anti-TNF-α-experienced patients.¹⁴ However, these conclusions derive from indirect comparisons across heterogeneous randomized trials.”

My take: Vedolizumab is a good choice as a 1st line agent for ulcerative colitis but has a lower success rate as a 2nd line agent. Also, this study likely underestimates the potential effectiveness of JAKi as most individuals received tofacitinib rather than upadacitinib.

Related blog posts:

• Prior Exposure to TNF Antagonists May Increase Response to JAK Inhibitors in Patients with Ulcerative Colitis
• Comparative Evidence and Positioning Advance Therapies for Inflammatory Bowel Disease
• Long-term Efficacy and Safety of Upadacitinib for Ulcerative Colitis
• Dr. Joel Rosh: Positioning Therapies for Pediatric Ulcerative Colitis
• Upadacitinib vs Ustekinumab for Ulcerative Colitis
• Comparative Safety of Advanced Therapies for Ulcerative Colitis
• Tofacitinib Outperformed Vedolizumab in Anti-TNF-experienced Ulcerative Colitis
• Upadacitinib for Pediatric Ulcerative Colitis
• Upadacitinib Works Quickly and with High Response
• IBD Updates: Preventing Inflammatory Bowel Disease with a Healthy Diet and Medication Safety Pyramid
• “Real-World” Experience: High Dose Upadacitinib Recaptures IBD Response

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