Abstract
In the past decade, advances in the understanding of the pathogenesis of inflammatory bowel disease have permitted the development of agents directed against rational therapeutic targets. In particular, various antagonists of tumor-necrosis factor-α have been developed. These include infliximab, adalimumab, certolizumab (CDP870), CDP571, etanercept, and onercept. Clinical trials of these agents have demonstrated varying degrees of clinical efficacy. The use of these agents can be limited by infection, immunogenicity, acute infusion reactions, delayed hypersensitivity reactions, and autoimmune phenomena. This review provides insights into the use of antagonists of tumor-necrosis factor-α for the treatment of inflammatory bowel disease.
Key Points
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Infliximab is effective in the induction and maintenance of clinical remission in luminal and fistulizing Crohn's disease, as well as in ulcerative colitis
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Adalimumab and certolizumab are effective in the induction and maintenance of clinical remission in Crohn's disease
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Potential limitations of the TNF-α antagonists include infection, infusion reactions, autoimmune phenomena, and immunogenicity
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The capacity to induce apoptosis of TNF-α-expressing cells and neutralization of TNF-α alone are insufficient for clinical efficacy in Crohn's disease
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Gary R Lichtenstein has served as a consultant to Abbott Corporation, AstraZeneca Inc., Axcan, Celltech Inc., Centocor Inc., Elan, Faro Pharmaceuticals, Human Genome Sciences, Proctor and Gamble, Prometheus Laboratories Inc., Protein Design Labs, Protomed Scientific, Salix Pharmaceuticals, Schering-Plough Corporation, Serono, Shire Pharmaceuticals, Smith Kline Beecham Corporation, Solvay Pharmaceuticals, Synta Pharmaceuticals, UCB, and Wyeth. He has received research support from Abbott Corporation, Berlex, Celgene Corporation, Celltech Inc., Centocor Inc., Genetics Institute, Human Genome Sciences, Inkine Inc., Intesco Corporation, ISIS Corporation, Millenium Pharmaceuticals, Otsuka Corporation, Protein Design Labs, Protomed Scientific, and Salix Pharmaceuticals. He has served on the Speakers Bureau for AstraZeneca, Axcan, Centocor Inc., Faro Pharmaceuticals, Proctor and Gamble, Salix Pharmaceuticals, Schering-Plough Corporation, Shire Pharmaceuticals, and Solvay Pharmaceuticals. He has received an honorarium from Falk Pharma.
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Chang, J., Lichtenstein, G. Drug Insight: antagonists of tumor-necrosis factor-α in the treatment of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 3, 220–228 (2006). https://doi.org/10.1038/ncpgasthep0447
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DOI: https://doi.org/10.1038/ncpgasthep0447
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