Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2026
Ustekinumab and Janus Kinase Inhibitors Outperform Vedolizumab as Second-Line Therapy in Anti-Tumor Necrosis Factor-Experienced Patients With Ulcerative Colitis.
СтатьяМногоцентровое исследованиеСравнительное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Privitera Giuseppe, Bezzio Cristina, Figlioli Gisella, D'Amico Ferdinando, Mendes Joao, Varca Simone, Zingone Fabiana, Rodriguez-Lago Iago, Onali Sara, Caprioli Flavio A, Chaparro María, Barreiro-de-Acosta Manuel, Karmiris Konstantinos, Degabli Natalie Tamir, Dar Lior, Pastorelli Luca, Gutiérrez Ana, Orlando Ambrogio, Zabana Yamile, Saibeni Simone, Piovani Daniele, Savarino Edoardo V, Pugliese Daniela, Magro Fernando, Danese Silvio, Armuzzi Alessandro, PODIUM Study Group
Аннотация
BACKGROUND & AIMS: With the advent of agents targeting distinct inflammatory pathways, therapeutic sequencing after anti-tumor necrosis factor alpha (TNF-α) failure in ulcerative colitis (UC) represents a major challenge. We compared the real-world effectiveness and safety of vedolizumab, ustekinumab, and Janus kinase inhibitors (JAKis) in anti-TNF-α-exposed patients.
METHODS: In this retrospective, multicenter European study, adults with UC initiating second-line vedolizumab, ustekinumab, or a JAKi after anti-TNF-α were evaluated. Baseline confounding was addressed by applying energy balancing weights (EBWs). Effectiveness outcomes included probability of steroid-free clinical remission (SFCR) and biochemical SFCR at 12 months, analyzed using EBW-weighted Royston-Parmar survival models to derive adjusted time-averaged hazard ratios (aHRs). Adverse event (AE) rates were compared using EBW-weighted Poisson regression.
RESULTS: A total of 596 patients were included (301 vedolizumab, 149 ustekinumab, 146 JAKi); 54.7% were male, with a mean age of 43.9 ± 15.5 years. Clinical activity, endoscopic scores, and biomarker levels were broadly comparable across treatment groups. Infliximab was the most common prior anti-TNF-α (74.8%), and secondary failure was the predominant discontinuation reason (47.3%). Compared with vedolizumab, both ustekinumab and JAKi showed significantly higher probability of SFCR (aHR, 1.54; 95% confidence interval [CI], 1.09-2.07; and aHR, 1.66; 95% CI, 1.07-2.53, respectively) and biochemical SFCR (aHR, 2.26; 95% CI, 1.48-3.28 and 3.37; 95% CI, 2.01-5.36, respectively) at 12 months, with no differences between them. JAKi recipients experienced an approximately 4-fold higher incidence of AEs, compared with both vedolizumab and ustekinumab, with no differences between ustekinumab and vedolizumab.
CONCLUSIONS: Ustekinumab and JAKi were more effective than vedolizumab in inducing steroid-free and biochemical remission following anti-TNF-α failure. Safety concerns with JAKi warrant careful patient selection in clinical practice.
CLINICALTRIALS: gov, Number: NCT06691061.
METHODS: In this retrospective, multicenter European study, adults with UC initiating second-line vedolizumab, ustekinumab, or a JAKi after anti-TNF-α were evaluated. Baseline confounding was addressed by applying energy balancing weights (EBWs). Effectiveness outcomes included probability of steroid-free clinical remission (SFCR) and biochemical SFCR at 12 months, analyzed using EBW-weighted Royston-Parmar survival models to derive adjusted time-averaged hazard ratios (aHRs). Adverse event (AE) rates were compared using EBW-weighted Poisson regression.
RESULTS: A total of 596 patients were included (301 vedolizumab, 149 ustekinumab, 146 JAKi); 54.7% were male, with a mean age of 43.9 ± 15.5 years. Clinical activity, endoscopic scores, and biomarker levels were broadly comparable across treatment groups. Infliximab was the most common prior anti-TNF-α (74.8%), and secondary failure was the predominant discontinuation reason (47.3%). Compared with vedolizumab, both ustekinumab and JAKi showed significantly higher probability of SFCR (aHR, 1.54; 95% confidence interval [CI], 1.09-2.07; and aHR, 1.66; 95% CI, 1.07-2.53, respectively) and biochemical SFCR (aHR, 2.26; 95% CI, 1.48-3.28 and 3.37; 95% CI, 2.01-5.36, respectively) at 12 months, with no differences between them. JAKi recipients experienced an approximately 4-fold higher incidence of AEs, compared with both vedolizumab and ustekinumab, with no differences between ustekinumab and vedolizumab.
CONCLUSIONS: Ustekinumab and JAKi were more effective than vedolizumab in inducing steroid-free and biochemical remission following anti-TNF-α failure. Safety concerns with JAKi warrant careful patient selection in clinical practice.
CLINICALTRIALS: gov, Number: NCT06691061.