P0398AI-enabled endoscopy and quantitative histology provide novel insights into relationship between macroscopic and microscopic inflammation in Ulcerative Colitis

Abstract Background In Ulcerative Colitis (UC) clinical trials, endoscopy and histology are complementary to evaluate disease activity. While endoscopy is the gold standard for assessing mucosal healing, histology is increasingly vital because microscopic inflammation can persist even with normal-appearing endoscopic findings. While the relationship between endoscopy and histology is highly correlated for patients with inactive and severe disease activity, the correlation is low for patients with mild and moderate disease 1. Here, we leverage artificial intelligence (AI)-enabled endoscopic and histologic tools to characterise disease activity in the high variance space of mild and moderate UC. Methods Retrospective data from LUCENT-1 (NCT03518086), a phase 3 UC induction trial of mirikizumab (a p19-targeted anti-interleukin-23), was analysed. Available patient data includes Mayo endoscopy scores (MES) from endoscopy procedure recordings and Geboes score (GS) from Haematoxylin and Eosin (H 3.1): for MES 1, the median involvement was 11% vs 0%, and for MES 2, 38% vs 20%, respectively (Figure 2A). Using IBDExplore, we found that the features measuring neutrophils across tissue regions and granulation tissue align with the endoscopic interpretation (Figure 2B). Conclusion We utilized AI tools to assess the histologic variability across mild to moderate MES in UC and demonstrate the granular connection between microscopic and macroscopic manifestations. We propose that these findings may dissect drivers of inflammation and mucosal barrier repair to characterise disease characteristics and predict response to treatment. Reference: 1. Lemmens B, Arijs I, Van Assche G, et al. Correlation Between the Endoscopic and Histologic Score in Assessing the Activity of Ulcerative Colitis: Inflammatory Bowel Diseases. 2013;19(6):1194-1201. doi:10.1097/MIB.0b013e318280e75f *AI-ESe is For Research Use Only. Not for use in diagnostic procedures. **IBDExplore is For Research Use Only. Not for use in diagnostic procedures. Conflict of interest: Reinisch, Walter: Personal Fees: WR has served as a speaker for AbbVie, Alfasigma, Celltrion, Ferring, JNJ, Galapagos Medice, Lilly, MSD, Roche, Pfizer, Sobi, Takeda, as a consultant for AbbVie, Agomab, Alfasigma, Alvotech, Amgen, Anaptys Bio, AOP Orphan, Boehringer Ingelheim, Bristol Myers Squibb, Calyx, Celltrion, Eli Lilly, Galapagos, Gilead, Index Pharma, Janssen, Medahead, Merck, Microbiotica, Pfizer, Sanofi, Teva, Takeda as an advisory board member for AbbVie, Alfasigma, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Galapagos, JNJ, Pfizer, Teva and has received research funding from AbbVie, JNJ, Sandoz, Sanofi, Takeda. Rubin, David T.: Grant support: Takeda Pharmaceuticals Consultant: Abbvie, Abivax SA, Altrubio, Athos Therapeutics, Inc, Bristol-Myers Squibb, Celltrion, Connect BioPharma, Eli Lilly & Co., Genentech (Roche) Inc., Iterative Health, Janssen Pharmaceuticals, Johnson & Johnson, Merck & Co., Mirador, Odyssey Therapeutics, Pfizer, Sanofi, Spyre, Takeda Pharmaceuticals, Vedanta Biosciences, and Ventyx. Gayda, David: DG is an employee of Eli Lilly and may hold stock or stock options in Eli Lilly. Taylor, Rhian: RT is an employee of Eli Lilly and may hold stock or stock options in Eli Lilly. Dr. Onken, Derek: DO is an employee of Eli Lilly and may hold stock or stock options in Eli Lilly. Colucci, Daniel: DC is an employee of Iterative Health and may hold stock or stock options in Iterative Health Jayson, Christina: CJ is an employee of PathAI and may hold stock or stock options in PathAI Thomason, Darren: DT is an employee of Iterative Health and may hold stock or stock options in Iterative Health Warr, Alyson R.: ARW is an employee of PathAI, may hold stock or stock options in PathAI, and is a stockholder in Kelonia Therapeutics Moses, Richard: RM is an employee of Eli Lilly and may hold stock or stock options in Eli Lilly. Lissoos, Trevor: TL is an employee of Eli Lilly and may hold stock or stock options in Eli Lilly. Other: Takeda Pharmaceuticals, USA Inc Gottlieb, Klaus: KG is a previous employee of Eli Lilly and may hold stock or stock options in Eli Lilly