The association between endoscopic and histological inflammation in ulcerative colitis

Klaus Theede, MD Gastrounit, Medical Division Copenhagen University Hospital Hvidovre Denmark

Disclosures

The study was supported by grants from AbbVie Inc.

Ferring Pharmaceuticals

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

Methods

• 76 patients comprising both active and inactive ulcerative colitis underwent sigmoideoscopy and rectal biopsies.

Endoscopic evaluation of the inflammation: • Mayo Endoscopic Score • Widely implemented in daily practice and clinical trials • Patients divided into 4 categories with increasing inflammatory activity • Ulcerative Colitis Endoscopic Index of Severity • Newly developed scoring system 1 • Composite system • 3 different descriptors • • • Vascular pattern Bleeding Presence of erosions/ulcers 1 Travis et al, GUT 2012

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 Cryptitis Crypt abscess Erosions/ulcers (absent vs. present)

0 (0 %) 1 (< 10 %) 2 (10 – 50 %) 3 (> 50 %)

Results

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

Results

3 4 5 6 7 8 9 10 Total

Mayo Endoscopic Score

0 1 2 3 Total 28 4 0 2 0 0 0 0 28 6 1 0 0 0 7 2 2 0 0 4 11 5 0 0 0 0 8 6 13 5 0 0 33 0 0 13 2 0 22 5 3 8 7 3 76 Gamma: 0.99, CI95% (0.98-1)

Results

0 1 2 3 Total

Mayo Endoscopic Score

0 1 2 3 Total 25 6 3 3 0 6 1 0 29 15 0 0 31 3 4 13 6 9 21 1 6 8 10 19 73 Gamma: 0.83, CI95% (0.70-0.95) 19 % 0 1 2 3 Total 3 23 4 0 0 27 0 5 4 2 3 0 4 8 5 2 1 1 2 1 6 1 2 6

UCEIS

7 0 3 4 6 13 1 5 8 0 2 2 4 6 9 1 0 1 10 0 0 0 3 3 Total 29 15 10 19 73 Gamma: 0.76, CI95% (0.63-0.89) 15 %

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

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

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