P710 Prevalence, Characteristics and Management of Patients with Difficult-To-Treat Inflammatory Bowel Disease: A Cross-Sectional Study From a Tertiary Referral Center

Abstract

Abstract Background Difficult-to-treat (D2T) inflammatory bowel disease (IBD) is defined by lack or loss of response to advanced treatments with 2 or more mechanisms of action (MoA), Crohn’s (CD) recurrence after 2 resections, chronic antibiotic refractory pouchitis, complex perianal CD or by the presence of psychiatric comorbidities impairing IBD management.1 We aimed to assess the prevalence, characteristics, management, and outcomes of D2T-IBD. Methods We retrospectively searched the electronic medical records of patients with IBD followed at San Raffaele Hospital (Milan, Italy) as of October 1st, 2023. Patients enrolled in clinical trials altering disease management were excluded. Results In total 679 patients with moderate-to-severe IBD were included (350 CD, 326 UC, 3 IBD-U). 163 patients (24%) met at least one criterion of D2T (25% CD, 23% UC). Of these, 75% did not respond or lost response to 2 or more biologics/small molecules with different MoA, 18% had complex perianal CD, 17% had CD recurrence after 2 or more resections for active CD, the remaining had antibiotic refractory pouchitis or psychiatric comorbidities impairing IBD management. Multiple criteria can coexist. Figure 1. Drug-wise, 54% of patients with D2T-IBD failed 2 MoA, 26% 3 MoA, and 3% 4 MoA, the remaining had other causes of D2T-IBD. Prevalence of D2T varied across phenotypes of CD. The presence of perianal disease doubled the probability of D2T-CD (48 vs 24%); stricturing (B2), fistulizing (B3), and upper gastrointestinal involvement (L4) also increased risk. In UC, 22% of left-sided colitis (E2) and 27% of pancolitis (E3) were D2T, no proctitis was D2T. Patients with D2T-CD had a longer mean disease duration (14 vs 8.7 years; p<0.05) and time on advanced treatments (78 vs 63 months; p<0.05). The same two analyses showed no significant difference for UC (11.6 vs 11.2 years; and 41 vs 50 months; both p>0.05). Differently from bio-naive patients (Figure 2A), patients with D2T-IBD were mostly on ustekinumab, followed by infliximab and adalimumab in CD, and by upadacitinib, infliximab and tofacitinib in UC. Notably, 11 patients with D2T-CD received a combination of advanced therapies. Figure 2B Overall, 61% of patients with D2T-IBD were in clinical remission, 43% in biochemical remission (calprotectin <150 μg/g), and 13% in endoscopic remission (Mayo≤1; or SES-CD≤3 or Rutgeerts i0-i1). Conclusion D2T-IBD is heterogeneous but most commonly due to multidrug failure and associated with certain phenotypes of IBD. Ustekinumab was the most common treatment choice for D2T-IBD. The majority of patients with D2T-IBD achieved clinical remission but failed to achieve biochemical or endoscopic remission. 1. Parigi et al. Lancet Gastroenterol. & Hep. 2023