title: 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.
abstract: OBJECTIVE
  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; pseudo R(2)=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.
authors.affiliation: Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Faubion
authors.forename: Joel G
authors.initials: JG
authors.lastname: Fletcher
authors.forename: Sharon
authors.initials: S
authors.lastname: O'Byrne
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
authors.forename: Willem Js
authors.initials: WJ
authors.lastname: de Villiers
authors.forename: Bruce
authors.initials: B
authors.lastname: Salzberg
authors.forename: Scott
authors.initials: S
authors.lastname: Plevy
authors.forename: Deborah D
authors.initials: DD
authors.lastname: Proctor
authors.forename: John F
authors.initials: JF
authors.lastname: Valentine
authors.forename: Peter D
authors.initials: PD
authors.lastname: Higgins
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Harris
authors.forename: Lauri
authors.initials: L
authors.lastname: Diehl
authors.forename: Lilyan
authors.initials: L
authors.lastname: Wright
authors.forename: Gaik Wei
authors.initials: GW
authors.lastname: Tew
authors.forename: Diana
authors.initials: D
authors.lastname: Luca
authors.forename: Karen
authors.initials: K
authors.lastname: Basu
authors.forename: Mary E
authors.initials: ME
authors.lastname: Keir
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D003113:Colonoscopy; D003424:Crohn Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D005243:Feces / Q000737:chemistry*; D005260:Female; D006801:Humans; D007378:Interleukins / Q000097:blood*; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D014057:Tomography, X-Ray Computed; D000097043:Interleukin-22
chemical_list: D015415:Biomarkers; D007378:Interleukins; D039841:Leukocyte L1 Antigen Complex; D020780:Matrix Metalloproteinase 9; D000097043:Interleukin-22