PMID- 16307694
OWN - NLM
STAT- MEDLINE
DCOM- 20060210
LR  - 20190911
IS  - 0300-7995 (Print)
IS  - 0300-7995 (Linking)
VI  - 21
IP  - 11
DP  - 2005 Nov
TI  - Endoscopic and histologic evidence of persistent mucosal healing and correlation 
      with clinical improvement following sustained infliximab treatment for Crohn's 
      disease.
PG  - 1741-54
AB  - OBJECTIVES: 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.
FAU - Geboes, Karel
AU  - Geboes K
AD  - Universitair Ziekenhuis St. Rafael, Afdeling Pathologie, Leuven, Belgium. 
      Karel.Geboes@uz.kuleuven.ac.be
FAU - Rutgeerts, Paul
AU  - Rutgeerts P
FAU - Opdenakker, Ghislain
AU  - Opdenakker G
FAU - Olson, Allan
AU  - Olson A
FAU - Patel, Kamlesh
AU  - Patel K
FAU - Wagner, Carrie L
AU  - Wagner CL
FAU - Marano, Colleen W
AU  - Marano CW
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Curr Med Res Opin
JT  - Current medical research and opinion
JID - 0351014
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Biomarkers)
RN  - 0 (Placebos)
RN  - B72HH48FLU (Infliximab)
SB  - IM
MH  - Adult
MH  - Animals
MH  - *Antibodies, Monoclonal/pharmacology/therapeutic use
MH  - Biomarkers/metabolism
MH  - Biopsy
MH  - *Crohn Disease/drug therapy/immunology/pathology
MH  - Endoscopy
MH  - Female
MH  - Humans
MH  - Infliximab
MH  - Intestinal Mucosa/drug effects/*pathology
MH  - Male
MH  - Placebos
MH  - Severity of Illness Index
MH  - Statistics as Topic
MH  - Wound Healing/*drug effects
EDAT- 2005/11/26 09:00
MHDA- 2006/02/14 09:00
CRDT- 2005/11/26 09:00
PHST- 2005/11/26 09:00 [pubmed]
PHST- 2006/02/14 09:00 [medline]
PHST- 2005/11/26 09:00 [entrez]
AID - 10.1185/030079905x65457 [doi]
PST - ppublish
SO  - Curr Med Res Opin. 2005 Nov;21(11):1741-54. doi: 10.1185/030079905x65457.