Integrating anti-tumor necrosis factor therapy in inflammatory bowel disease: Current and future perspectives

Crohn's disease and ulcerative colitis are two idiopathic inflammatory diso rders of the GI tract. Manifestations of disease can be severe and lead to long term therapy with a variety of medications and/or surgery. Standard me dical therapy consists of agents that either treat suppurative complication s or modulate the inflammatory cascade in a nonspecific manner. Many specif ic chemokine and cytokine effecters that promote intestinal inflammation ha ve been identified. Such work has led to experimental clinical trials with a variety of cytokine antagonists. Compounds directed against one such cyto kine, tumor necrosis factor a (TNF), have demonstrated the greatest clinica l efficacy to date. This is consistent with scientific observations that su ggest a central role for TNF in the inflammatory cascade. Infliximab is a c himeric monoclonal antibody against TNF that has been demonstrated to be ef fective for the treatment of Crohn's disease. Infliximab is Food and Drug A dministration approved for the treatment of Crohn's disease. There exist se veral other TNF antagonists in various phases of investigation, including t he monoclonal antibody CDP 571, the fusion peptide etanercept, the phosphod iesterase inhibitor oxpentifylline, and thalidomide. The clinical efficacy of these agents and the role of TNF in the pathogenesis of inflammatory bow el disease is reviewed.