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RESPONSE TO BIOLOGICS IN IBD PATIENTS ASSESSED BY COMPUTERIZED IMAGE ANALYSIS OF PROBE BASED CONFOCAL LASER ENDOMICROSCOPY WITH MOLECULAR LABELING

Presentation Number: Fr596

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AuthorBlock: Marietta Iacucci3, Enrico Grisan1, Nunzia Labarile3, Olga Maria Nardone3, Samuel Charles Lloyd Smith3, Louisa Jeffery3, Rosanna Cannatelli3, Subrata Ghosh3, Andrea Buda2
1School of Engineering, London South Bank University, London, London, United Kingdom; 2Department of Gastrointestinal Oncological Surgery, S. Maria del Prato Hospital, Feltre, Italy, Feltre, Italy; 3Institute Translational of Medicine, Institute of Immunology and Immunotherapy and NIHR Birmingham Biomedical Research Centre, University Hospitals NHS Foundation Trust and University of Birmingham, Birmingham, UK, Birmingham, United Kingdom;

Abstract Body
Background The increase in therapeutic choices in inflammatory bowel diseases (IBD) imposed the identification of personalized therapeutic strategy. Confocal laser endomicroscopy (CLE) is a new endoscopic tool developed to obtain virtual in vivo histology. The aim of this study was to identify CLE in vivo and ex vivo features predictive of response for patients planned to receive biologics by using computerized image analysis.

Methods We performed a prospective observational study at a single tertiary referral centre. 29 IBD patients (14 ulcerative colitis-UC and 15 Crohn’s Disease-CD) underwent colonoscopy with CLE before and after starting anti -TNF or anti α4β7 integrin. CLE parameters analyzed were: crypt distribution along the mucosal surface, crypt area (CA), eccentricity, diameter, inter-cryptic distance (ICD), vessel tortuosity (VT), fluorescein leakage through the colonic mucosa (FLCM). Ex-vivo binding activity of fluorescein labelled biologics on corresponding biopsies was also assessed. Mosaicism reconstruction of CLE images were analyzed using a dedicated software algorithm (CellvizioViewer, Mauna Kea Technologies, ParisFrance). A dedicated Graphical User Interface was designed to enable a semiautomated analysis.

Results After treatment, VT resulted significantly changed in overall IBD population(p<0.05), FLCM were reduced in UC patients (p<0.05), whilst CA, eccentricity and ICD decreased in CD patients (p< 0.05). The univariate regression analysis identified FLCM as the most accurate parameter for predicting responsiveness (AUROC) 83%, accuracy 83%, positive predictive value-PPV 94% and negative predictive value-NPV 57%). FLCM and ICD were the best discriminants in responders Vs non responders in UC patients (AUROC 85%, accuracy 85%, PPV 100% and NPV 71%); whilst VT, CA and ICD in CD patients (AUROC 95%, 86% and 83%; accuracy 90%, 90% and 88%; PPV 100%, 100% and 86%; and NPV 75%, 75% and 100%, respectively). Ex vivo confocal imaging revealed that UC patients, especially those responders, had higher basal fluorescent intensity signals with a significant reduction after biological treatment (p< 0.05), whereas in CD patients no significant change was found. An increased mucosal binding to the fluorescent labelled biological agent was associated to a higher likelihood of response to the treatment; this effect was higher in UC patients (AUROC 81%, accuracy 77%, PPV 100%, NPV 63%) compared to CD patients (AUROC 64%, accuracy 79%, PPV 80%, NPV 50%).

Conclusion We report novel in vivo morphological and functional changes of crypt and microvasculature architecture pre and post biological treatment. FLCM and ICD were the best discriminants of response in UC patients, while VT, CA and ICD in CD patients. A higher mucosal binding to a biological agent before treatment was observed in responders for UC patients but not in CD patients.