Am J Gastroenterol  2001 Jul;96(7):1977-97 

Integrating anti-tumor necrosis factor therapy in inflammatory bowel disease:

current and future perspectives.

Blam ME, Stein RB, Lichtenstein GR.

Department of Medicine, Hospital of the University of Pennsylvania, University

of Pennsylvania School of Medicine, Philadelphia 19104-4283, USA.

Crohn's disease and ulcerative colitis are two idiopathic inflammatory disorders

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 medical therapy

consists of agents that either treat suppurative complications or modulate the

inflammatory cascade in a nonspecific manner. Many specific chemokine and

cytokine effectors that promote intestinal inflammation have been identified.

Such work has led to experimental clinical trials with a variety of cytokine

antagonists. Compounds directed against one such cytokine, tumor necrosis factor

alpha (TNF), have demonstrated the greatest clinical efficacy to date. This is

consistent with scientific observations that suggest a central role for TNF in

the inflammatory cascade. Infliximab is a chimeric monoclonal antibody against

TNF that has been demonstrated to be effective for the treatment of Crohn's

disease. Infliximab is Food and Drug Administration approved for the treatment

of Crohn's disease. There exist several other TNF antagonists in various phases

of investigation, including the monoclonal antibody CDP 571, the fusion peptide

etanercept, the phosphodiesterase inhibitor oxpentifylline, and thalidomide. The

clinical efficacy of these agents and the role of TNF in the pathogenesis of

inflammatory bowel disease is reviewed.