Biological agents therapy in crohn's disease

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) with significant morbidity and health care costs. The disease seems to occur when the intestinal immune cascade is triggered by microbial antigens in genetically susceptible individuals. Over-activation of the enteric immune and inflammatory pathways causes mucosal damage resulting in the clinical signs and symptoms. Various medications, including 5-aminosalicylates, antibiotics, corticosteroids, and immune-modulators have traditionally been used to control inflammation. Their use is intended to prevent surgery and improve the patient's quality of life, but none cure the disease. Unfortunately, many patients require steroids to control their symptoms and a wide range of dose-related adverse effects makes this an unappealing strategy. Immune-modulators are effective maintenance drugs, but have a slow onset of action with clinical remission rates of approximately 40%. Recently, biological therapy has brought a paradigm shift in the management of CD and other autoimmune diseases, such as rheumatoid arthritis, psoriatic arthritis and multiple sclerosis (MS), resulting in marked decrease of disability and improvement in quality of life. Biologic therapies encompass agents with diverse modes of action, including the tumor necrosis factor a (TNFa) inhibitors, such as infliximab and adalimumab, that are the monoclonal antibody-based therapy of choice in CD. Natalizumab, an adhesion molecule inhibitor, is also used in refractory CD. Although the remarkable efficacy of biological therapy has resulted in significant success in CD management, serious side effects do occur, necessitating careful monitoring of therapy. In addition to other well documented neurologic, hematologic, immunologic, cardiovascular and malignant adverse effects, biological agents therapy has been associated with the development of serious life-threatening infections. In particular, the human polyomavirus JC (JCV) reactivation in CD after biological therapy and its association with progressive multifocal leukoencephalopathy (PML) has been found in one patient treated with natalizumab. After this case of PML and other two cases in MS patients, commercial and investigational use of natalizumab was suspended in February 2005 but was subsequently resumed for MS and for CD, only through a special restricted distribution program to patients who had refractory disease and who have failed both immune-suppressants and anti-TNFa agents and who have careful screening and subsequent monitoring for JCV infection. Therefore, this chapter will address an immunological overview of CD physiopathology, followed by the focusing on the use of infliximab, adalimumab and natalizumab in CD, and on their side effects, with particular attention to the issue of JCV reactivation. © 2013 Nova Science Publishers, Inc. All rights reserved.