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Title: NOD2/CARD15 does not influence response to infliximab in Crohn's disease
Authors: Vermeire, Severine ×
Louis, Edouard
Rutgeerts, Paul
De Vos, Martine
Van Gossum, Andre
Belaiche, Jacques
Pescatore, Paul
Fiasse, Rene
Pelckmans, Paul
Vlietinck, Robert
Merlin, Françoise
Zouali, Habib
Thomas, Gilles
Colombel, Jean-Frederic
Hugot, Jean-Pierre #
Issue Date: Jul-2002
Series Title: Gastroenterology vol:123 issue:1 pages:106-11
Abstract: BACKGROUND & AIMS: NOD2/CARD15 was recently identified as the first gene underlying Crohn's disease (CD) susceptibility. Monoclonal antibodies to tumor necrosis factor (TNF)-alpha (infliximab) are a potent treatment for CD, with about 70% of patients responding. It is not clear which factors influence treatment outcome. We assessed whether variants in NOD2/CARD15 are predictive for differences in clinical response. METHODS: Two hundred forty-five CD patients (86 fistulizing, 159 luminal) receiving infliximab in an expanded access program were genotyped for the 3 main associated variants of NOD2/CARD15, without knowledge of the treatment response. Short-term clinical response was assessed at 4 weeks (refractory) or 10 weeks (fistulizing) after first infliximab infusion, and the mean duration of response was calculated. In a subgroup of patients, production of TNF in response to lipopolysaccharide (LPS) in mucosal biopsy tissue was also determined by means of immunoassay, and results were related to the different NOD2/CARD15 genotypes. RESULTS: In total, 32.6% of patients carried mutations in NOD2/CARD15 (18.8% R702W, 8.6% G908R, and 10.2% 1007fs) compared with 15% in controls (P < 0.001). Despite observed differences in TNF production in mucosal biopsy tissue, there was no relationship between the overall presence of a mutation in NOD2/CARD15 or of any of the mutations separately and short-term infliximab response or response duration. Furthermore, multivariate analysis could not identify clinical characteristics that, in combination with NOD2/CARD15 mutations, were associated with response to infliximab. CONCLUSIONS: In this cohort of CD patients, the frequency of NOD2/CARD15 mutations was significantly greater than that of healthy controls. However, NOD2/CARD15 was not predictive of treatment outcome with infliximab in CD.
URI: 
ISSN: 0016-5085
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Research in GastroIntestinal Disorders
Clinical Genetics Section (-)
× corresponding author
# (joint) last author

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