Background: Biologics and small-molecule therapies are widely used for ulcerative colitis (UC), but their comparative effectiveness in anti-tumor necrosis factor (TNF)-exposed patients is unclear. Objectives: To compare the effectiveness and safety of vedolizumab, ustekinumab, and tofacitinib in anti-TNF-experienced patients with UC. Design: Multicenter retrospective observational cohort study. Methods: A multicenter retrospective cohort of anti-TNF-experienced UC patients treated with vedolizumab ( n = 260), tofacitinib ( n = 149), or ustekinumab ( n = 193) was analyzed. Partial Mayo Score (pMayo), endoscopic remission, and biomarker response were assessed at baseline, 12, 24, and 52 weeks, respectively. Inverse Probability of Treatment Weighting (IPTW) was applied to balance baseline characteristics, and longitudinal changes were analyzed using repeated-measures general linear models with post hoc corrections. Results: After IPTW adjustment, at week 52, clinical remission was highest with tofacitinib compared with ustekinumab ( p < 0.001) and vedolizumab ( p = 0.002). Steroid-free clinical remission showed a similar pattern (tofacitinib vs ustekinumab: p = 0.006; tofacitinib vs vedolizumab: p < 0.001). No significant differences in biochemical remission were found across groups at week 52 ( p = 0.931). Endoscopic remission favored vedolizumab over ustekinumab and tofacitinib ( p < 0.001). Subgroup analyses revealed superior tofacitinib performance in extensive colitis and in patients with ⩾2 prior biologic classes (vs vedolizumab: p = 0.089; vs ustekinumab: p < 0.001). Adverse events were infrequent and similar across groups. Conclusion: In anti-TNF-experienced UC patients, tofacitinib was associated with higher long-term clinical and steroid-free remission rates, ustekinumab showed intermediate effectiveness with a favorable safety profile, while vedolizumab was associated with higher endoscopic remission. These findings may help inform individualized, outcome-oriented treatment strategies, but they should be interpreted with caution and confirmed in prospective head-to-head studies.
Tursi et al. (Fri,) studied this question.