Abstract Background Inflammatory bowel disease (IBD), can progress into clinically complex forms requiring advanced therapeutic approaches. In recent years, the concept of “Difficult to Treat” (DTT) has emerged to describe patients with persistent inflammatory activity. This phenotype includes patients with failure of multiple treatment lines with different mechanisms of action, postoperative recurrence following repeated intestinal resections, chronic antibiotic-refractory pouchitis, complex perianal disease, or psychosocial factors that interfere with adherence or treatment effectiveness. This group represents a high-risk population. The aim of this study was to characterize the DTT phenotype in Mexican IBD patients and identify associated factors. Methods A retrospective observational study was conducted at a referral center in Mexico City in a cohort of patients with a diagnosis of IBD. A total of 175 patients were included, and those fulfilling the proposed clinical criteria for the DTT phenotype were identified. Descriptive statistics, bivariate analyses, and binary logistic regression were applied to identify factors associated with the DTT phenotype. Results Of the 175 patients, 83 (47.4%) were women and 92 (52.6%) men; 117 (66.9%) had UC and 58 (33.1%) CD. The mean age was 54 ± 17.31 years, with a mean age at diagnosis of 44 ± 17.80 years and a mean disease duration of 11 (1–52) years. A total of 43 patients (24.6%) met at least one DTT criterion: 39 (90.7%) had failed two biologics with different mechanisms of action, 3 (7.0%) had postoperative recurrence in CD, 1 (2.3%) developed refractory pouchitis, and 1 (2.3%) had complex perianal disease.DTT patients showed a significantly younger current age (p 0.001; Δ = –10.2 years; d = –0.61) and a younger age at diagnosis (p = 0.004; Δ = –8.9 years; d = –0.51)Table 1. In logistic regression analysis, none of the variables were statistically significant predictors of meeting DTT criteria. Within the DTT group, 34 (79.0%) received a biologic or small molecule, 8 (18.6%) used combination advanced therapies, and only 1 (2.3%) remained on conventional treatment. Regarding treatment lines, 24 (57.1%) were on second-line therapy, 11 (26.2%) on third-line, 4 (9.5%) on fourth-line, 2 (4.8%) on fifth-line, and 1 (2.4%) on sixth-line. Conclusion One quarter of IBD patients met DTT criteria, with failure to multiple biologics being the most frequent finding. These patients had a significantly younger age at diagnosis and at the time of study. These results may reflect the fact that this research was conducted at a referral center. The findings highlight the importance of early identification of patients at risk of a complex disease course to optimize management. References: 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. 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. Caron B, Habert A, Bonsack O, et al. Difficult-to-treat inflammatory bowel disease: effectiveness and safety of 4th and 5th lines of treatment. United European Gastroenterol J. 2024;12(5):605-613. Conflict of interest: Parra Holguín, Norma Nathaly: No conflict of interest Lopez Gomez, Jesus Gerardo: No conflict of interest Haro Limón, Mariana: No conflict of interest Ramírez Tebalán, Byron Daniel: No conflict of interest García Alonso, Daniela Alejandra: No conflict of interest Cortés Espinosa, Tomás: No conflict of interest
Holguín et al. (Thu,) studied this question.