The role of pharmacogenomics in the prediction of efficacy of anti-TNF therapy in patients with Crohn's disease

TNF-alpha plays a central role in the pathophysiology of Crohn's disease. Infliximab, a chimeric monoclonal antibody against TNF-alpha, has been shown to be effective and well-tolerated in several large placebo-controlled trials and has become a common treatment for Crohn's disease. The blockade of TNF through the infusion of infliximab is characterized by high clinical efficacy and rapid onset of action. A single infusion of infliximab results in a remission rate of 30-40%. Lack of response appears to be a stable trait even after repeated infusions, suggesting that it might be genetically determined. Mutations in the TNF-alpha gene have been extensively studied as predictors of response with various results. Polymorphisms in the TNF-alpha receptors TNF-R1 and TNF-R2 have been found not to be associated with treatment response. Similarly, the three mutations in the CARD15 gene, which are independently associated with susceptibility to Crohn's disease, have also been found not to be associated with treatment response.