Real-life effectiveness and safety of tofacitinib and vedolizumab as 2nd-line for ulcerative colitis after anti-TNFs: A multicenter cohort IGIBD study (VE2TO-UC)

Background and aims: Drug positioning in ulcerative colitis (UC) patients refractory to anti-tumor necrosis factor (TNF) is still debated. In a nationwide multicentre observational cohort, we aimed to compare the real-life effectiveness and safety of tofacitinib and vedolizumab as second-line for UC after anti-TNFs. Methods: Disease activity was evaluated at weeks 8, 26, and 52 ± 4. The primary outcome was to compare clinical remission (partial Mayo score (PMS) ≤2 with no subscore >1) at week 26. Secondary outcomes included comparative effectiveness for corticosteroid-free clinical remission (CFCR); biochemical, endoscopic, and histologic remission; combined corticosteroid-free clinical-objective remission; and treatment persistence. Inverse probability of treatment weighting was used for all comparisons. Results: Overall, 134 tofacitinib- and 277 vedolizumab-treated UC patients were included. At week 26, no difference was observed between tofacitinib and vedolizumab for clinical remission (adjusted odds ratio [aOR]: 0.9; 95 % confidence interval [CI]: 0.6 – 1.6). At week 8, tofacitinib was more effective in achieving CFCR (aOR: 1.7; 95 % CI: 1.0 – 2.7). Clinical, biochemical, endoscopic, and histologic outcomes showed no difference between tofacitinib and vedolizumab at weeks 26 and 52. In patients with baseline PMS ≥ 2, steroid use, or anti-TNF non-response no difference was found for clinical remission at week 26. Tofacitinib-treated patients were more likely to discontinue treatment (adjusted Hazard Ratio: 1.8; 95 % CI: 1.2 – 2.8). Safety was consistent with treatment profiles in UC. Conclusions: Tofacitinib and vedolizumab were equally effective and safe as second-line therapy in anti-TNFs experienced UC patients. Tofacitinib showed greater efficacy in inducing CFCR at week 8, but carried higher discontinuation risk.