Prevalence, Clinical Characteristics, and Predictors of Difficult-to-Treat Inflammatory Bowel Disease in a Real-World...

A subset of patients with inflammatory bowel disease (IBD) remains refractory to treatment despite multiple lines of advanced therapies. These patients are often categorized as having difficult-to-treat (DTT) IBD. We retrospectively analyzed 354 patients with IBD (including 112 with Crohn's disease [CD] and 242 with ulcerative colitis [UC]) from a real-world cohort. Baseline demographic and disease characteristics, treatment history, and outcomes were compared between the DTT-IBD and non-DTT-IBD groups. Logistic regression analysis was performed to identify factors associated with DTT-IBD in CD and UC cohorts. Approximately 10.6% of the patients exposed to advanced therapy fulfilled the definition of DTT-IBD (CD: 9.8%, UC: 11.4%). Compared with patients with non-DTT-IBD, those with DTT-IBD exhibited a significantly higher exposure to multiple biologic classes, including antitumor necrosis factor (94.1% vs. 59.0%), anti-integrin (94.1% vs. 47.2%), anti-interleukin-12/23 (88.2% vs. 19.4%), and Janus kinase inhibitors (35.3% vs. 0.7%). The DTT-IBD group had a significantly lower clinical remission rate at the last follow-up than the non-DTT-IBD group (52.9% vs. 85.4%, p = 0.001). A longer interval from diagnosis to the initiation of advanced therapy was independently associated with DTT-IBD in CD (OR: 1.014 per month, 95% CI: 1.001-1.026, p = 0.026). No significant predictors for UC were identified. In conclusion, DTT-IBD, characterized by extensive biologic exposure and suboptimal long-term remission rates, accounts for approximately 10% of patients with IBD receiving advanced therapy. In CD, delayed initiation of advanced therapy may contribute to refractoriness. These findings emphasize the unmet need for earlier therapeutic intervention, better predictive markers of treatment response, and novel therapeutic mechanisms.