title: Tumor necrosis factor blockade for treatment of inflammatory bowel disease: efficacy and safety.
abstract: Inflammatory bowel disease (IBD), including Crohn's Disease (CD) and Ulcerative Colitis (UC), is characterized by inflammation of the gastrointestinal tract. In UC, inflammation is confined to the mucosa, initially involving the rectum, and may extend proximally to involve the entire colon. In CD, transmural inflammation may affect any portion of the GI tract. The etiology of these disease processes has remained unclear. Therapies are aimed at reducing inflammation and thereby improving symptomatology and morbidity. Traditional medical therapies have included corticosteroids, aminosalicylates, and immunomodulators. Within the past decade, another class of medications has been utilized targeting Tumor Necrosis Factor (TNF), a key, early signaling molecule in the inflammatory cascade. Increased levels of TNF have been found in the blood, epithelial tissue, and stool of patients with active IBD. Anti-TNF medications can not only have direct effects on immune system components, but they also can ameliorate apoptotic cell death and tight junction compromise in the gastrointestinal epithelium. Several randomized, placebo controlled studies have demonstrated the efficacy of these medications in achieving induction and maintaining remission of disease. Their safety profile, however, remains a concern. There has been a reported association of biologic therapy and increased opportunistic infections. A link between biologic therapy and the development of certain malignancies has also been described. Despite these associations, TNF blockade remains an important therapeutic development in the modern therapy of IBD. The role of barrier breakdown at the tight junction level in IBD, and of TNF induction of barrier disruption, is also discussed.
authors.affiliation: Department of Gastrointestinal Medicine, Lankenau Hospital, GI Fellows Office, 1(st) Floor, 100 E. Lancaster Ave., Wynnewood, PA 19096, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ngo
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Farrell
authors.forename: Maura
authors.initials: M
authors.lastname: Barr
authors.forename: Kevin
authors.initials: K
authors.lastname: Wolov
authors.forename: Robert
authors.initials: R
authors.lastname: Bailey
authors.forename: James M
authors.initials: JM
authors.lastname: Mullin
authors.forename: James J
authors.initials: JJ
authors.lastname: Thornton
mesh_terms: D000068879:Adalimumab; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068582:Certolizumab Pegol; D002986:Clinical Trials as Topic; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D000069285:Infliximab; D011092:Polyethylene Glycols / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007140:Immunoglobulin Fab Fragments; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D000069285:Infliximab; D000068879:Adalimumab; D000068582:Certolizumab Pegol