Introduction: anti-TNF strategies in the treatment of Crohn's disease.

Abstract

For several years, researchers have recognized the existence of a relationship between disorders of the immune system and the occurrence and evolution of inflammatory bowel disease. Although the aetiology of inflammatory bowel disease remains unknown, there is a growing body of evidence suggesting that chronic bowel inflammation results from abnormalities in the mucosal immune system. In patients with inflammatory bowel disease, there may exist an imbalance between pro-inflammatory and anti-inflammatory mediators. Tumour necrosis factor-alpha, a pro-inflammatory cytokine, has been identified as a key mediator in the pathogenesis of Crohn’s disease. The use of a therapy specifically target-ing such pro-inflammatory mediators could induce re-mission and dramatically influence disease evolution. Successful treatment of patients with Crohn’s disease includes three essential components: (1) induction and maintenance of disease remission; (2) promotion of healing of the mucosal epithelium; (3) prevention of complications (post-operative relapse, stenosis, fistulae, poor nutrition) associated with the disease. Achievement of these goals should result in the normali-zation of patients’ quality of life. Standard pharmacologic therapies currently available for treatment (i.e. 5-amino-salicylate formulations, antibiotics, corticosteroids, immunosuppressive agents) are able to control disease in only a proportion of patients and, except for immunosuppressive agents, most are not active in the long term. In addition, many are associated with potential toxicity. Prior to the commencement of the annual meeting of the World Congress of Gastroenterology, a symposium entitled New Advances in Inflammatory Bowel Disease: A Focus on Infliximab was convened. The goal of the symposium was to provide gastroenterologists with a comprehensive update on the clinical efficacy and safety of infliximab (cA2) in the treatment of Crohn’s disease. Key issues relative to the emerging role of infliximab in the context of current treatment and clinical practices were presented by key researchers in the field of inflammatory bowel disease. The initial presentation by Dr Sander van Deventer reviewed the mediators and cellular constituents involved in the inflammatory process underlying Crohn’s disease, the mechanism of action of infliximab, and the potential effect of therapy with the chimeric monoclonal antibody on the mucosal immune system. Data on the efficacy and safety of infliximab in clinical trials in patients with Crohn’s disease were presented by Drs Paul Rutgeerts and Stephen Hanauer. Results from a recently completed trial with infliximab treating patients with fistulizing Crohn’s disease were summarized by Dr Daniel Present. In this trial, infliximab was documented as the first therapeutic agent demonstrating efficacy in a placebo-controlled trial in fistula closure in patients with Crohn’s disease complicated by fistulae. Finally, Dr Brian Feagan reported on the various costs associated with inflammatory bowel disease, the reduced quality of life for patients afflicted with the disease, and the potential and relevant economics issues related to the use of infliximab. Although debilitating and presently incurable, advancements in the treatment of inflammatory bowel disease with novel biologic therapies such as infliximab continue to ensure new practices for treatment and new avenues for dramatically improving patient outcomes and quality of life.