P752 Difficult-to-treat inflammatory bowel disease: effectiveness and safety of 4th and 5th lines

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Abstract Background Many patients with inflammatory bowel disease (IBD) have signs or symptoms of active disease despite multiple treatment attempts. This emerging concept is defined difficult-to-treat IBD. The objective of this study was to investigate for the first time treatment persistence, efficacy and safety of biologics or small molecules used in 4th or 5th line therapy. Methods We reviewed all consecutive patients with IBD treated at Nancy University Hospital between July 2022 and April 2023 with the 4th or 5th line treatment for at least three months. The primary outcome was to assess the persistence rate of 4th and 5th line therapy. Results We enrolled 82 patients with IBD (4th line: 44; 5th line: 38). On Kaplan-Meier analysis the duration of risankizumab, ustekinumab or vedolizumab therapy did not differ significantly (p>0.05) as 4th and 5th line treatment. The restricted mean survival time analysis showed that persistence rate of risankizumab was the highest as 4th line therapy (risankizumab vs. vedolizumab: 36.0 and 29.4 weeks respectively, p=0.008; risankizumab vs. ustekinumab: 36.0 and 32.8 weeks respectively, p=0.035). In multivariate regression, Crohn’s disease diagnosis (Odd ratio 4.6; 95% confidence interval 1.7-12.4) was significantly associated with treatment persistence. Conclusion In this first real-world setting, risankizumab could have longer persistence rate as 4th line treatment for IBD than other agents. Persistence of biological agents was greater in Crohn’s disease than in ulcerative colitis. More studies are needed to compare treatment efficacy in patients with difficult-to-treat IBD.