Abstract Background Vedolizumab (VDZ) is widely used as first-line advanced therapy in patients with moderate-to-severe ulcerative colitis (UC). However, data guiding optimal sequencing for patients with prior non-response to VDZ are limited. We aimed to compare the effectiveness of second-line therapies by evaluating the 12-week response rate and 1-year persistence for each medication. Methods This retrospective study, included UC patients from 6 Greek centers, who initiated a second-line therapy following prior VDZ failure were included. The primary outcome was clinical response at week 12, defined as a decrease in the Simple Clinical Colitis Activity Index (SCCAI) of ≥ 2 points from baseline, along with the one-year persistence of each medication. Endoscopic response was defined as a decrease in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) of ≥ 2 points from baseline. Clinical remission was defined as SCCAI ≤2, and endoscopic remission as UCEIS = 0. x2, t-test and the Mann–Whitney U test.were used for categorical, normally distributed continuous variables and non-normally distributed ones respectively. One-way ANOVA was used to compare means across multiple groups. Kaplan–Meier plots were used to depict treatment persistence. Results 90 patients (47 males, 52.2%; mean age 39.6 years) were included in the study. 23 patients (25.6%) had received dose intensification of VDZ before switching to another agent. Second-line therapies included infliximab (IFX, n = 55), ustekinumab (UST, n = 16), tofacitinib (TOFA, n = 7), upadacitinib (UPA, n = 4), ozanimod (OZA, n = 3), and Risankizumab (RIZ, n = 1); Comparisons were performed only between the IFX and UST groups, given the limited sample size of the other groups. These patients did not differ significantly in baseline characteristics (Table 1). Clinical response rates were: IFX 33/55 (60%), UST 11/16 (68.8%), TOFA 4/7 (57.1%), OZA 2/3 (66.7%), UPA 4/4 (100%), and RIZ 1/1 (100%). One-year persistence rates were: IFX 28/51 (54.9%), UST 8/15 (53.3%), TOFA 4/7 (57.1%), UPA 4/4 (100%), OZA 2/2 (100%), and RIZ 1/1 (100%). No significant differences between IFX and UST in either clinical response (p = 0.526) or 1-year persistence (p = 0.915) were found (Figure 1). Median duration of treatment was similar between IFX (12 months) and UST (12.5 months, p = 0.609). Importantly, nearly all patients who achieved a clinical response at week 12 continued their therapy for at least one year. Conclusion Among UC patients who failed first-line VDZ, IFX and UST showed comparable effectiveness and one-year persistence. TOFA and UPA demonstrated similar efficacy, although the analysis was limited by small sample sizes. Nearly all patients with clinical response in week 12 remained on the same treatment for one year. Conflict of interest: Markopoulos, Panagiotis: None Kokkotis, Georgios: No conflict of interest Agorogianni, Alexandra: No conflict of interest Gkolfou, Ioanna: No conflict of interest Pardalis, Pavlos: no conflicts Vachliotis, Ilias: No conflict of interest Varka, Alexandra: No conflict of interest Axiaris, Georgios: No conflict of interest Giouleme, Olga: No conflict of interest Michopoulos, Spyridon: None Soufleris, Konstantinos: No conflict of interest Tsironi, Eftychia: No conflict of interest Viazis, Nikolaos: Nothing to declare Zampeli, Evanthia: I have received honor-aria and speaker fees from Abbvie, Janssen, Pfizer,Takeda, MSD, AMGEN, Genesis, Ferring, Mylan, BMS, Galenica Bamias, Giorgos: Grants: Grants from Takeda, AbbVie, Mylan/Viatris/Biocon, Genesis Pharma, Ferring, Vianex, and Aenorasis Consulting Fees and Speaker Honoraria: AbbVie, Adacyte Therapeutics, Amgen, Bristol Myers Squibb, Faran, Ferring, Galenica, Genesis Pharma, J&J, Lilly, MSD, Mylan/Viatris/Biocon, Pfizer, Shattuck Labs, Takeda, Vianex-
Markopoulos et al. (Thu,) studied this question.