Efficacy and Safety of Second‐Line Advanced Therapy After Vedolizumab in Ulcerative Colitis: A Multicenter Cohort Study From the GETAID

ABSTRACT Background and Aims Vedolizumab has become the preferred first‐line advanced therapy in ulcerative colitis (UC). However, the optimal second‐line treatment following vedolizumab failure remains unclear. We aimed to evaluate the effectiveness and safety of second‐line therapies after first‐line vedolizumab. Methods We conducted a multicenter retrospective study including UC patients from 31 centers who received infliximab (IFX), subcutaneous (SC) anti‐TNFs, or ustekinumab after vedolizumab failure. The primary endpoint was steroid‐free clinical remission (SFCR) at week 14. Predictors of remission were identified using multivariate logistic regression. Results Among 196 patients, 99 received IFX, 27 anti‐TNF SC, and 70 ustekinumab. At week 14, SFCR was achieved in 78 patients (39.8%): 38 (38.4%) with IFX, 8 (29.6%) with anti‐TNF SC, and 32 (45.7%) with ustekinumab, with no significant difference between groups ( p = 0.32). Median treatment persistence ranged from 8 to 9.2 months. Baseline corticosteroid use was associated with lower odds of SFCR (OR = 0.37, 95% CI 0.18–0.73). Adverse events occurred in 15.8% of patients, including 12.2% serious events. Overall adverse events were less frequent with ustekinumab than with IFX (10.0% vs. 24.2%, p = 0.02), while serious events were comparable (5.7% vs. 16.1%, p = 0.08). Discontinuation due to adverse events was more frequent with IFX (12.1%) and anti‐TNF SC (14.8%) than with ustekinumab (2.9%, p = 0.045 and 0.049). Conclusion In UC patients failing vedolizumab, second‐line IFX, anti‐TNF SC, and ustekinumab showed similar effectiveness and persistence. Infliximab remains a robust option for rapid control in high inflammatory burden, whereas ustekinumab may be preferred for its superior safety profile in high‐risk patients.