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Superior Effectiveness of Upadacitinib Over Tofacitinib and Ustekinumab in Bio-Exposed Ulcerative Colitis: The
Joana Camões Neves1, Dalila Costa1, Margarida Cristiano2
1Gastroenterology Department, Unidade Local de Saúde Braga, Braga, Portugal; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
Background & Aims:
Despite the progress in advanced therapies (ATs) for ulcerative colitis (UC), selecting a second-line treatment after failure remains challenging. Recent guidelines recommend upadacitinib, tofacitinib, or ustekinumab as high-efficacy options after prior AT failure. However, real-world comparative data among these 3 agents are lacking.
Methods:
This was a retrospective multicenter study (9 centers) including patients with UC who failed ≥1 AT. Patients were stratified into upadacitinib, tofacitinib, or ustekinumab groups and assessed at weeks 16 and 52. The primary outcome was steroid-free clinical remission (SFCR), and secondary outcomes included biochemical and endoscopic remission. Weighted outcomes were analyzed using multivariable logistic regression after propensity score-based inverse probability weighting.
Results:
We evaluated 312 patients (57.1% female [n = 178]; mean age at diagnosis, 32.6 ± 8.4 years) who initiated upadacitinib (n = 103; 33.0%), tofacitinib (n = 74; 23.7%), or ustekinumab (n = 135; 43.3%). The SFCR rates at weeks 16 and 52 were 47.6% and 75.0% for upadacitinib, 27.0% and 52.4% for tofacitinib, and 26.7% and 53.4% for ustekinumab. The corresponding endoscopic remission rates were 38.1% and 56.8%, 13.2% and 32.7%, and 24.6% and 22.5%. After propensity score-based inverse probability weighting, upadacitinib was associated with higher odds of SFCR compared with tofacitinib (week 16: odds ratio [OR], 2.56; 95% confidence interval [CI], 1.16-5.64; week 52: OR, 3.14; 95% CI, 1.22-8.12) and ustekinumab (week 16: OR, 3.71; 95% CI, 1.88-7.29; week 52: OR, 4.68; 95% CI, 1.96-11.18). Upadacitinib outperformed tofacitinib (week 16: OR, 7.44; 95% CI, 2.09-26.53; week 52: OR, 3.51; 95% CI, 1.22-10.12) and ustekinumab (week 16: OR, 3.34; 95% CI, 1.38-8.09; week 52: OR, 8.69; 95% CI, 3.07-24.60) for endoscopic remission at both timepoints.
Conclusions:
Upadacitinib showed higher effectiveness than tofacitinib and ustekinumab in bio-experienced patients with UC.
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