P0625TRIDENT-UC Study: Higher Efficacy Medication in Bio-Exposed Ulcerative Colitis Patients

Abstract Background Despite the progress in advanced therapies (AT) for ulcerative colitis (UC), selecting a second-line treatment after failure remains challenging. Recent guidelines recommend Ustekinumab (UST), Tofacitinib (TOFA), or Upadacitinib (UPA) as high-efficacy options after prior AT failure. However, no real-world studies have compared all three therapies simultaneously. Methods Retrospective multicentre study (9 centres) of UC patients who failed ≥1 AT. Patients were stratified into UST, TOFA, or UPA groups and assessed at 16 and 52 weeks. The primary outcome was steroid-free clinical remission (SFCR) based on the Patient Reported Outcomes-2. Secondary outcomes included biochemical remission based on faecal calprotectin levels and endoscopic remission (Mayo Endoscopic Subscore = 0). A subanalysis assessed only second-line therapy after anti-TNF failure. Multivariable models were adjusted for demographics, disease activity and prior treatments. Results We evaluated 312 patients 57.1% female (n = 178); mean age at diagnosis 32.6 ± 8.4 years who initiated UST (n = 135; 43.3%), UPA (n = 103; 33.0%), or TOFA (n = 74; 23.7%). Baseline disease duration and extent were comparable across groups, and 53.2% (n = 166) had failed ≥2 prior advanced therapies. In the multivariate model, at week 16, UPA had 4 times higher odds of achieving SFCR than UST (OR 3.89; p 0.001) and 2 times compared to TOFA (OR 2.31; p = 0.016). At week 52, UPA showed 3 times higher odds of SFCR than UST (OR 3.34; p = 0.003) and than TOFA (OR 2.72; 0.039). UPA also achieved higher endoscopic remission at week 16 and 52 compared to UST (16w: OR 2.47; p = 0.036; 52w: OR 5.95; p 0.001) and TOFA (16w: OR 5.42; p = 0.001; 52w: OR 2.64; p = 0.049). Post-hoc comparisons from the linear mixed-effects model showed that UPA achieved a higher reduction in faecal calprotectin than UST (p 0.001) and TOFA (p = 0.044). In the subanalysis, UPA was superior to both UST (OR 3.00; p = 0.009) and TOFA (OR 6.11; p = 0.005) in achieving the primary outcome. Conclusion Even though all three medication demonstrated high efficacy in bio-exposed UC patients, UPA achieved better results at week 16 and 52 in this real-world study. Reference: Singh, Siddharth, et al. “AGA living clinical practice guideline on pharmacological management of moderate-to-severe ulcerative colitis.” Gastroenterology 167.7 (2024): 1307-1343. Conflict of interest: Ms. Camões Neves, Joana: No conflict of interest Costa, Dalila Amélia Amorim: No conflict of interest Cristiano, Margarida: No conflict of interest Portela, Francisco: consulting fees and support from the following companies: Abbvie, Falk, Ferring, Janssen, Lilly, Pfizer, Pharmakern, Takeda and Tillots. Fernandes, Ana Rita: No conflict of interest Fernandes, Samuel Raimundo: No conflict of interest Portugal, Margarida: No conflict of interest Gututui, Madalina: No conflict of interest Paulo, João Pedro: No conflict of interest Gonçalves, Nuno: No conflict of interest Fernandes, Daniela: No conflict of interest Costa, Catarina: No conflict of interest Madureira, Ana Rita: No conflict of interest Vaz Conde, Patrícia: No conflict of interest Damasceno, José: No conflict of interest Guimaraes, Andreia: No conflict of interest Arroja, Bruno: No conflict of interest Goncalves, Raquel: No conflict of interest Leal, Tiago Filipe: No conflict of interest