Antibodies to tumor necrosis factor-α in the treatment of Crohn's disease

Crohn's disease is characterized by acute and chronic intestinal inflammation, and can involve any part of the gastrointestinal tract. The most frequently involved areas of the intestine (the terminal ileum and colon) have higher bacterial loads than the rest of the intestine, suggesting a role for a dysregulated immune response to luminal bacteria. Research into the pathogenesis of Crohn's disease using animal models supports a role for Th1-mediated immune responses, and inhibition of the generation of a Th1 response is known to prevent disease. Based on these observations, antitumor necrosis factor-alpha (anti-TNFalpha) therapies have been used to treat patients with Crohn's disease and more recently with ulcerative colitis. Certain anti-TNFa therapies, such as infliximab, have resulted in dramatic clinical responses in patients with Crohn's disease. Other therapies such as etanercept, however, have not been effective. In this review we will discuss the different strategies that have been employed to inhibit TNFalpha and their relative merits. We will also address factors that predict response to therapy such as concurrent immunomodulators, high C-reactive protein expression, and polymorphisms in the Fcgamma receptor.