Frequency and Risk Factors for Difficult-to-Treat Inflammatory Bowel Disease among Patients Receiving Advanced Therapies in a Korean Tertiary-Care Cohort

Background/Aims: Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), show variable treatment responses. Data on the prevalence and clinical predictors of difficult-to-treat IBD (DTT-IBD) among Asians receiving advanced therapies (ATs) remain limited. This study evaluated the proportion of DTT-IBD and its risk factors in a Korean IBD cohort. Methods: We conducted a retrospective analysis of a prospectively maintained tertiary-care cohort including patients with UC or CD who received at least one AT. Kaplan-Meier analysis, log-rank tests, and Cox proportional hazards regression were used to identify factors associated with DTT-IBD. DTT-IBD was defined as multidrug failure (MF; failure after ≥2 ATs with different mechanisms) or multiple resections (MR; recurrence after ≥2 intestinal resections in CD patients). Results: Among 512 patients, 130 (25.4%) met the MF DTT-IBD criteria. The cumulative probability of MF increased from 5.3% at 1 year to 51.1% at 10 years in UC patients, and from 0.4% to 37.1% in CD patients. Starting ATs within 2 years of UC diagnosis and older age increased the risk of MF DTT-IBD. In CD patients, risk factors included older age and vedolizumab as first-line AT. Among CD patients undergoing a second surgery, the cumulative risk of MR DTT-IBD reached approximately 50% at 1 year, 86.4% at 5 years, and >93% at 10 years. Conclusions: MF DTT-IBD occurred in one-quarter of patients. Timing of AT initiation and age in UC and therapy type and age in CD patients were key predictors. High MR DTT-IBD risk in CD patients underscores the need for proactive monitoring and early strategies.