P1036 Persistence of biologics and advanced small molecules in 4th, 5th and 6th line of therapy for inflammatory bowel disease: a cross-sectional retrospective study

Abstract

Abstract Background The choice of treatment for inflammatory bowel disease (IBD) with multiple prior drug failures, also known as difficult-to-treat (D2T) IBD, is an increasing challenge. We assessed the persistence of biologics and advanced small molecules, a surrogate for their efficacy, in patients with Crohn's disease (CD) and ulcerative colitis (UC) overall and in 4th, 5th and 6th lines of advanced treatment. Methods We retrospectively searched the electronic medical records of patients with IBD followed at the San Raffaele Hospital (Milan, Italy) up to 1 October 2023. Patients enrolled in clinical trials that changed disease management or receiving experimental drugs were excluded. Drug persistence was defined as the time from initiation to discontinuation of each treatment. Welch's ANOVA and Games-Howell's method for multiple comparisons were used. Results A total of 679 patients with moderate to severe IBD were included. 350 had CD, 326 UC, and 3 IBD-U. The mean disease duration was 11 years and 452 (66%) had received 5-aminosalicylates or antimetabolites as first maintenance treatment. Escalation to and changes between advanced treatments over time is summarised in Figure 1A. A greater use of anti-TNF agents was observed in the first lines of treatment whereas newer medications were proportionally more prescribed in refractory patients. In the overall analysis, regardless of the line of treatment, there was no difference in drug persistence between agents at 12 months (p=0.62), with approximately half of the patients having discontinued the drug. Figure 1B In subsequent lines of treatment, drug persistence decreased significantly in patients with CD (p=0.002). The trend was particularly pronounced from line 2, with a mean duration of 31 months, to line 7, with a mean duration of 11 months. In UC, the reduction was less evident and borderline non-significant (p=0.05), although it suggests a decrease in drug efficacy as the disease progresses. Figure 2 A, B In patients with D2T IBD, drug persistence in 4th, 5th and 6th line advanced treatment was similar for all agents (all p>0.05), indicating no clear advantage of one drug over the others. Figure 2 C, D, E Conclusion In CD, and possibly in UC, the persistence of patients on any advanced drug decreases with subsequent lines of treatment. None of the advanced agents showed a longer persistence time when used as a 4th, 5th or 6th line of treatment.