Comparative effectiveness and safety of upadacitinib versus vedolizumab in anti-TNF-exposed patients with ulcerative colitis
Jian Wan, Hao Zhang, Xiaojie Yuan, Zhengyu Ren, Sumei Sha, Changyue Wu, Yingchao Li, Xin Liu, Xin Wang, Jiaming Zhou, Chuhan Hu, Fei Chen, Min Chen, Jie Liang, Kaichun WuAbstract
Background & Aims
Head-to-head comparative evidence between upadacitinib and vedolizumab for anti-tumor necrosis factor (TNF)-exposed ulcerative colitis (UC) patients is lacking. This study compared their real-world effectiveness and safety.
Methods
This multicenter retrospective cohort included anti-TNF-exposed UC patients with a partial adapted Mayo score ≥ 2 who received upadacitinib or vedolizumab between March 2021 and February 2026 and had a minimum of 16 weeks of follow-up. Clinical outcomes were assessed at weeks 16 and 26, with endoscopic evaluation at week 26. The primary outcome was steroid-free symptomatic remission (SFSR) at week 16, defined as rectal bleeding subscore = 0 and stool frequency subscore ≤ 1, with no corticosteroid use for at least 2 weeks prior to assessment. Propensity score-based inverse probability of treatment weighting (IPTW) was used to adjust for imbalance of baseline characteristics.
Results
A total of 242 patients were analyzed (120 vedolizumab, 122 upadacitinib). After IPTW, upadacitinib was superior in achieving week-16 SFSR (71.7% vs 54.6%; adjusted odds ratio [aOR] 2.11, 95% CI, 1.67-2.65, P < .001). At week 26, upadacitinib remained superior in SFSR (82.6% vs 61.8%; aOR 2.93, 95% CI, 1.85-4.66, P < .001) and also demonstrated higher rates of endoscopic improvement (75.3% vs 47.1%; aOR 3.42, 95% CI, 2.57-4.56, P < .001), and endoscopic remission (41.5% vs 22.2%; aOR 2.49, 95% CI, 1.71-3.63, P < .001). There was no significant difference regarding the risk of drug discontinuation between the two groups (aHR 0.46, 95% CI, 0.20-1.04, P = .058). However, the overall incidence of adverse events was higher with upadacitinib (0.475 vs 0.213 per person-year, P < .001), while the rates of serious adverse events were not significantly different between groups.
Conclusions
Upadacitinib demonstrates superior effectiveness over vedolizumab in anti-TNF-exposed UC but carries a higher burden of adverse events, highlighting the need for personalized benefit-risk assessment to guide treatment selection.