Prevalence, characteristics, management, and outcomes of difficult-to-treat inflammatory bowel disease

Background and Aims: Criteria for "difficult-to-treat"inflammatory bowel disease (DTT-IBD) have recently been proposed to standardize terminology. We aimed to evaluate the prevalence, characteristics, management, and outcomes of DTT-IBD. Methods: We conducted a retrospective study in 2 tertiary centers in Italy. Results: Among 1736 IBD patients treated with biologics/advanced small molecules, 430 (24.8%) met at least 1 DTT-IBD criterion, of which 331 (77%) failed at least 2 mechanisms of action. In ulcerative colitis (UC), left-sided and extended colitis were risk factors for DTT compared to proctitis (odds ratio [OR] 6.55; 95% confidence interval [CI], 1.93-40.98; p=0.011 and OR 10.12; 95% CI, 3.01-63.14; p=0.002, respectively). In Crohn's disease (CD), multiple localizations (L3+L4) (OR 3.04; 95% CI, 1.09-8.34; p=0.03), stricturing (OR 2.24; 95% CI, 1.52-3.34; p<0.001), and penetrating (OR 2.33; 95% CI, 1.55-3.53; p<0.001) behaviors, and perianal disease (OR 2.49; 95% CI, 1.75-3.53; p<0.001) were the main risk factors for DTT. Delay in advanced treatment initiation was positively associated with DTT-CD (OR 1.74; 95% CI, 1.27-2.41; p=0.001) but protective in UC (OR 0.65; 95% CI, 0.45-0.93; p=0.019). The rates of symptomatic, biochemical, and endoscopic remission were lower in DTT-IBD compared to non-DTT-IBD. The difference was most evident for endoscopic remission (25% vs 62%). Drug persistency in each following line of treatment progressively decreased in CD and UC. All advanced drugs used in DTT-IBD had similar persistence. Conclusions: DTT-IBD was prevalent in approximately one-quarter of patients with IBD in a tertiary care setting. Certain IBD phenotypes and the delay in initiating treatment in CD were risk factors for DTT. Drug persistency decreased progressively with every subsequent line of therapy.