P1164Prevalence and Risk Factors of Difficult-to-Treat Inflammatory Bowel Disease in Crete

Abstract Background Despite major advances in Inflammatory Bowel Disease (IBD) management, a subset of patients remains difficult to treat (D2T) due to refractoriness, intolerance to multiple advanced therapies, or disease-related complications. We aimed to investigate the prevalence and risk factors associated with D2T-IBD. Methods Data from a prospective longitudinal IBD registry at University Hospital of Heraklion, Crete were analyzed. Adult patients with ulcerative Colitis (UC), or Crohn’s disease (CD) who had received at least once advanced therapy were included. D2T status was defined as: (1) failure of advanced treatments with ≥2 different mechanisms of action (MOA); (2) postoperative recurrence after ≥2 IBD-related surgical resections; (3) chronic, antibiotic-refractory pouchitis; and/or (4) complex perianal disease. Non-D2T patients served as the comparison group. Demographic and clinical characteristics as well as potential risk factors for D2T IBD were evaluated. Results Among 676 IBD patients 66.7% CD, 58.6% male, median (IQR) age 49 (37.7-62) years, 406 (59.7%) had received at least one advanced treatment. The median (IQR) time to first advanced treatment was 4 (0-10.25) years and 94 patients (23.1%) met at least one D2T criterion. Regarding D2T criteria, 44.6% fulfilled the multi-MOA failure definition, 13.8% had postoperative recurrence after ≥2 surgeries, 2.1% chronic antibiotic-refractory pouchitis, and 50% had complex perianal disease (Table 1). Among D2T CD patients, the most common used treatments were Infliximab and Adalimumab (30% and 29%), followed by Ustekinumab (11%). In D2T UC patients Ustekinumab (22%), Upaticitinib (19%) and Infliximab (19%) were most frequently used. In the multi-MOA failure group, Upadacitinib (24.4%) was the most common current therapy, followed by Infliximab (17.1%) and Ustekinumab (14.6%). Compared with non-D2T patients, those with D2T were diagnosed at a younger age (26 vs. 34 years; p = 0.0036), were more often male (69% vs. 55.4%; p = 0.018) and had a longer exposure to advanced therapies (10 vs. 6.5 years: p = 0.017). They also had higher rates of IBD related surgeries, and a lower prevalence of family history of IBD (all p 0.05). Penetrating phenotype and perianal disease were more common in D2T-CD patients (Table 1). Conclusion In this tertiary IBD cohort, nearly one-quarter of biologic experienced patients met at least one criterion for difficult-to-treat disease. In the multi-MOA failure group of patients JAK inhibitors seem to have an emerging role. Particular attention should be given to younger male patients, and those requiring surgery, as they are more likely to develop D2T disease. References: 1. Parigi TL, D’Amico F, Abreu MT, et al. Difficult-to-treat inflammatory bowel disease: results from an international consensus meeting. Lancet Gastroenterol Hepatol. 2023;8(9):853-859. doi:10.1016/S2468-1253(23)00154-1 2. Parigi TL, Massimino L, Carini A, et al. Prevalence, Characteristics, Management, and Outcomes of Difficult-to-Treat Inflammatory Bowel Disease. J Crohns Colitis. 2025;19(3):jjae145. doi:10.1093/ecco-jcc/jjae145 Conflict of interest: Mr. Chlorakis, George: No conflict of interest Orfanoudaki, Eleni: No Drygiannakis, Ioannis: No conflict of interest Foteinogiannopoulou, Kalliopi: No conflict of interest Koutroubakis, Ioannis E.: No conflict of interest