1. The association between endoscopic and histological inflammation in ulcerative colitis Klaus Theede, MD Gastrounit, Medical Division Copenhagen University Hospital Hvidovre Denmark

2. Disclosures The study was supported by grants from AbbVie Inc. Ferring Pharmaceuticals

3. Mucosal healing Mucosal healing has emerged as a key treatment goal in ulcerative colitis making endoscopy an important part of disease monitoring Endoscopic evaluation of treatment response is now widely recommended Histological acute inflammation despite endoscopic mucosal healing is present in some patients and carries an increased risk of relapse 1+2 1 Riley et al, GUT, 1991 2 Bessissow et al, Am J Gastroenterol, 2012

4. Methods 76 patients comprising both active and inactive ulcerative colitis underwent sigmoideoscopy and rectal biopsies. 1 Travis et al, GUT 2012 Endoscopic evaluation of the inflammation: Ulcerative Colitis Endoscopic Index of Severity Newly developed scoring system 1 Composite system 3 different descriptors Vascular pattern Bleeding Presence of erosions/ulcers Mayo Endoscopic Score Widely implemented in daily practice and clinical trials Patients divided into 4 categories with increasing inflammatory activity

5. Methods Sections from the biopsies were evaluated by two independent “blind” pathologists for the inflammatory activity using a four-point grading system (0-3), which included extent of cryptitis and crypt abscesses as well as the presence of erosions/ulcers. The chronicity of the inflammation was not evaluated 0 (0 %) 1 (< 10 %) 2 (10 – 50 %) 3 (> 50 %) Cryptitis Crypt abscess Erosions/ulcers (absent vs. present)

6. Results Age (years)38 (19-76) Gender Male Female 32 (42 %) 44 (58 %) Disease duration (years)5 years (0.0-48.5) Endoscopic activity Active (Mayo = 1-3) Inactive (Mayo = 0) 45 (59.2 %) 31 (40.8 %) Disease extent Proctitis Procto-sigmoiditis Left-sided or pancolitis 15 (33 %) 10 (22 %) 20 (44 %)

7. Results Mayo Endoscopic Score UCEIS 0123Total 328000 442006 517008 602406 70211013 800505 900257 1000033 Total331322876 Gamma: 0.99, CI95% (0.98-1)

8. Results UCEIS Histology 345678910Total 023221001029 14312320015 20012421010 30041614319 Total275861356373 Mayo Endoscopic Score Histology 0123Total 02530129 1636015 2036110 3049619 Total311321873 Gamma: 0.76, CI95% (0.63-0.89) Gamma: 0.83, CI95% (0.70-0.95) 15 % 19 %

9. Conclusion Strong, significant association between Mayo Endoscopic Score and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Significant association between histological inflammation and the endoscopic grade of inflammation evaluated with both Mayo Endoscopic Score and Ulcerative Colitis Endoscopic Index of Severity

10. Conclusion Histological inflammation in 15 -19 % of the patients with endosopic mucosal healing residual inflammation from previous active disease? medical treatment? special phenotype? These patients seems to have a higher rate of relapse – we need to obtain biopsies routinely to identify these patients when endoscopy reveals mucosal healing

11. Acknowledgments and disclosures Co-workers Susanne Holck, MD, DMSc 1 Per Ibsen, MD 1 Inge Nordgaard-Lassen, MD, DMSc 2 Anette Mertz Nielsen, MD, DMSc 2 1 Department of Pathology, Copenhagen University Hospital Hvidovre, Denmark 2 Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Denmark