Antitumor necrosis factor therapy for inflammatory bowel disease: A reviewof agents, pharmacology, clinical results, and safety

Citation
Wj. Sandborn et Sb. Hanauer, Antitumor necrosis factor therapy for inflammatory bowel disease: A reviewof agents, pharmacology, clinical results, and safety, INFLAMM B D, 5(2), 1999, pp. 119-133
Citations number
80
Categorie Soggetti
Gastroenerology and Hepatology
Journal title
INFLAMMATORY BOWEL DISEASES
ISSN journal
10780998 → ACNP
Volume
5
Issue
2
Year of publication
1999
Pages
119 - 133
Database
ISI
SICI code
1078-0998(199905)5:2<119:ANFTFI>2.0.ZU;2-M
Abstract
Tumor necrosis factor-alpha (TNF alpha), a proinflammatory cytokine, plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Biotechnology agents including a chimeric monoclonal anti-TNF antibody (inf liximab), a humanized monoclonal anti-TNF antibody (CDP571), and a recombin ant TNF receptor fusion protein (etanercept) have been used to inhibit TNF alpha activity. Controlled trials have demonstrated efficacy for infliximab in moderately to severely active Crohn's disease (CD) and fistulizing CD s ufficient to justify recent U.S. Food and Drug Administration (FDA) approva l. Additional trials have been completed in rheumatoid arthritis (RA). Simi larly, preliminary controlled trials have suggested efficacy for CDP571 in active CD and RA. Larger controlled trials have demonstrated efficacy for e tanercept in RA patients who have failed disease modifying antirheumatic dr ug (DMARD) therapy leading to FDA approval for RA. Toxicities observed with anti-TNF therapies have included formation of human antichimeric antibodie s (HACA) with associated acute and delayed hypersensitivity infusion reacti ons, human antihuman antibodies (HAHAs), and formation of autoantibodies wi th rare instances of drug-induced lupus. Several cases of non-Hodgkin's lym phoma also has been described. Future studies should evaluate optimal timin g and duration of anti-TNF therapy, the utility of adjuvant medical treatme nts during anti-TNF therapy, and evaluate long-term safety and efficacy of the various anti-TNF agents.