S1975 GLP1-RA in Patients With Crohn's Disease Independently Associated With Reduction in SEMA-CD Score

Introduction: Obesity in adults with inflammatory bowel disease (IBD) has been associated with increased risk of persistent disease activity in both Crohn’s Disease (CD) and Ulcerative Colitis (UC). Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RA) are not only associated with weight loss but also with reduced systemic inflammation. This study aimed to describe endoscopic outcomes of patients with IBD treated with GLP-1RA. Methods: We conducted a retrospective review of electronic health records, at a tertiary care center, from January 2018-January 2025. Adult patients with a history of CD or UC who were treated with GLP-1RA, for at least 3 months, were included. Patients received GLP-1RA therapy for either obesity or diabetes. The primary outcome was change in endoscopic disease activity, measured via SEMA-CD or Mayo score, one year prior to and one year post GLP-1RA therapy. Multivariable linear regression modeling was used to evaluate factors contributing to change in endoscopic disease activity. Co-variables included age, sex, change in IBD therapy and initiation of steroids (PO or IV). Results: We identified 180 CD and 174 UC patients treated with GLP1-RA. The majority received either semaglutide (57%) and were female (64%). Among the cohort, 32 (8.9%) patients had a documented CRP within 1 year prior to GLP-1RA as well as 6-12 months after with mean improvement of 7.1 mg/L (P = 0.045). Amongst patients with CD, 23 (6.4%) had endoscopic data with a mean improvement in SEMA-CD score of 1.22 (P = 0.047). On multivariable regression, adjusting for IBD therapy change and steroid initiation, we found that patients with CD on GLP-1RA exhibited a 5.05 point reduction in SEMA-CD score compared to CD patients not on GLP1RA therapy (P = 0.004). In this regression, initiation of steroids was also associated with reduction in SEMA-CD score (P = 0.003). This same improvement in disease activity was not seen in the UC cohort with endoscopic data available (n = 22; 6.1%), with a reduction in Mayo score of 0.14, not significant (P = 0.5). Conclusion: This study revealed an independent association between GLP-1RA therapy and improvement in SEMA-CD score, after taking into account change in IBD therapy (biologic change or escalation) and initiation of steroids (PO or IV). This study further supports the use of GLP-1RA therapy as an adjuvant therapy, for obesity or diabetes, in the IBD patient population with potential for optimization of inflammation.