NOD2/CARD15 Does Not Influence Response to Infliximab in Crohn's Disease

Background & Aims: NOD2/CARD15 was recently identified as the first gene underlying Crohn's disease (CD) susceptibility. Monoclonal antibodies to tumor necrosis factor (TNF)-α (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 N0D2/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 N0D2/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 N0D2 / CARD15 genotypes. Results: In total, 32.6 % o