Endoscopic and histologic evidence of persistent mucosal healing and correlation with clinical improvement following sustained infliximab treatment for Crohn's disease.
OBJECTIVE
The long-term effect of infliximab on endoscopic and histologic disease activity and expression of inflammatory markers was assessed in Crohn's disease patients who received infliximab as episodic or scheduled maintenance therapy therapy over 54 weeks (ACCENT 1).


METHODS
All patients received Infliximab 5 mg/kg at week 0 and at week 2 were then randomized as responders or nonresponders to placebo or infliximab (5 or 10mg/kg). Patients received placebo or infliximab 5 mg/kg at weeks 2 and 6 followed by placebo or infliximab (5 or 10mg/kg) every 8 weeks or episodically on loss of response. Crohn's Disease Activity Index (CDAI), Crohn's Disease Endoscopic Index of Severity (CDEIS), Inflammatory Bowel Disease Questionnaire (IBDQ), and colonic and ileal Global Histologic Disease Activity (CGHAS and IGHAS) scores were determined at weeks 0, 10, and 54. Tumor necrosis factor-alpha (TNF-alpha), gelatinase B, Infliximab, tenascin, clusters of differentiation marker 68 (CD68), and intercellular adhesion molecule-1 (ICAM-1) were detected in mucosal biopsies by immunohistochemistry.


RESULTS
At baseline, CDEIS significantly correlated with CGHAS only. Further at baseline, both CDEIS and the worst CGHAS or IGHAS, were significantly correlated with CD68, ICAM-1, and gelatinase B expression. At week 10, improvement in CGHAS only, correlated significantly with better CDAI, CDEIS, and IBDQ scores. Improvements in CDEIS and GHAS at week 10 correlated with reductions in gelatinase B and CD68, whereas only GHAS improvement correlated with decreased TNF-alpha expression. At week 54, decreased gelatinase B expression continued to correlate with improved CDEIS and GHAS while decreased CD68 and TNF-alpha expression correlated with GHAS and CDEIS improvement, respectively.


CONCLUSIONS
Endoscopic and histologic evidence of mucosal healing was associated with a sustained reduction in the expression of inflammatory markers. Infliximab-induced improvement in the clinical signs and symptoms of Crohn's disease was associated with endoscopic and histologic evidence of sustained mucosal healing.
Geboes
Karel
K
Universitair Ziekenhuis St. Rafaël, Afdeling Pathologie, Leuven, Belgium. Karel.Geboes@uz.kuleuven.ac.be
Rutgeerts
Paul
P
Opdenakker
Ghislain
G
Olson
Allan
A
Patel
Kamlesh
K
Wagner
Carrie L
CL
Marano
Colleen W
CW
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D003424:Crohn Disease / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D004724:Endoscopy; D005260:Female; D006801:Humans; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology*; D008297:Male; D010919:Placebos; D012720:Severity of Illness Index; D013223:Statistics as Topic; D014945:Wound Healing / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D010919:Placebos; D000069285:Infliximab