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EMerging BiomARKers in Inflammatory Bowel Disease (EMBARK) Study Identifies Fecal Calprotectin, Serum MMP9, and Serum IL-22 as a Novel Combination of Biomarkers for Crohn's Disease Activity: Role of Cross-Sectional Imaging

Faubion, William A Jr MD1; Fletcher, Joel G MD2; O'Byrne, Sharon MD3; Feagan, Brian G MD4; de Villiers, Willem JS MD5; Salzberg, Bruce MD6; Plevy, Scott MD7; Proctor, Deborah D MD8; Valentine, John F MD9; Higgins, Peter D MD, PhD10; Harris, Jeffrey M MD, PhD3; Diehl, Lauri DVM, PhD3; Wright, Lilyan PhD3; Tew, Gaik Wei MSc3; Luca, Diana PhD3; Basu, Karen PhD3; Keir, Mary E PhD3

American Journal of Gastroenterology: December 2013 - Volume 108 - Issue 12 - p 1891–1900
doi: 10.1038/ajg.2013.354
Inflammatory Bowel Disease

OBJECTIVES: In Crohn's disease (CD), clinical symptoms correspond poorly to inflammatory disease activity. Biomarkers reflective of mucosal and bowel wall inflammation would be useful to monitor disease activity. The EMBARK study evaluated disease activity in patients with ulcerative colitis (UC) and CD, and used endoscopy with or without cross-sectional imaging for biomarker discovery.

METHODS: UC (n=107) and CD (n=157) patients were characterized and underwent ileocolonoscopy (ICO). A subset of CD patients (n=66) also underwent computed tomography enterography (CTE). ICO and CTE were scored by a gastroenterologist and radiologist who incorporated findings of inflammation into a single score (ICO-CTE) for patients that underwent both procedures. Serum and fecal biomarkers were evaluated for association with the Mayo Clinic endoscopy score in UC patients and with ICO alone or ICO-CTE in CD patients. Individual biomarkers with a moderate degree of correlation (P≤0.3) were evaluated using multivariate analysis with model selection using a stepwise procedure.

RESULTS: In UC, ordinal logistic regression using Mayo Clinic endoscopy subscore selected the combination of fecal calprotectin and serum matrix metalloproteinase 9 (MMP9; pseudoR2=0.353). In CD, we found that use of the ICO-CTE increased specificity of known biomarkers. Using ICO-CTE as the dependent variable for biomarker discovery, the selected biomarkers were the combination of fecal calprotectin, serum MMP9, and serum IL-22 (r=0.699).

CONCLUSIONS: Incorporation of both ICO and CTE into a single measure increased biomarker performance in CD. Combinations of fecal calprotectin and serum MMP9 for UC, and combinations of fecal calprotectin, serum MMP9, and serum interleukin-22 in CD, demonstrated the strongest association with imaging/endoscopy-defined inflammation.

1 Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA

2 Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA

3 Research and Early Development, Genentech, South San Francisco, California, USA

4 Robarts Research Institute, University of Western Ontario, London, Ontario, Canada

5 Division of Digestive Diseases and Nutrition, University of Kentucky, Lexington, Kentucky, USA

6 Atlanta Gastroenterology Specialists, Atlanta, Georgia, USA

7 Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina, USA

8 Department of Medicine, Section of Digestive Diseases, Yale University, New Haven, Connecticut, USA

9 Division of Gastroenterology, Hepatology, and Nutrition, University of Utah, Salt Lake City, Utah, USA

10 Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA

Correspondence: William A. Faubion Jr, MD, Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA. E-mail:

Received 27 February 2013; accepted 3 September 2013

published online 15 October 2013

© The American College of Gastroenterology 2013. All Rights Reserved.
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