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Recent advances in basic science
Biologics in inflammatory bowel disease: how much progress have we made?
  1. W J Sandborn,
  2. W A Faubion
  1. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
  1. Correspondence to:
    Dr W J Sandborn
    Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA; sandborn.williammayo.edu

https://doi.org/10.1136/gut.2003.025452

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    INTRODUCTION

    Biologic therapies include:(1) naturally occurring or modified biologic compounds such as vaccines (live, live attenuated, or killed microorganisms), hormone extracts, and blood products;(2) recombinant proteins or peptides—for example, granulocyte macrophage colony stimulating factor and growth hormone;(3) monoclonal antibodies and fusion proteins; and (4) antisense oligonucleotides to nucleic acids. These biologic therapies, which are targeted towards specific disease mechanisms, have the potential to provide more effective and safe treatments for human diseases. Clinical trials have demonstrated that inhibition of the cytokine tumour necrosis factor α(TNF) and inhibition of the selective adhesion molecules α4 integrin and α4β7 integrin are effective in the treatment of various forms of the inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn’s disease (CD). It is also clear that drug toxicity related to biologic therapy, including hypersensitivity, serum sickness, autoimmunity, infection, and immunogenicity may occur. This article reviews the progress made to date in the treatment of IBD with biologic therapies, concentrating primarily on the TNF inhibitors infliximab, etanercept, adalimumab, CDP870, CDP571, and onercept, and on the selective adhesion molecule inhibitors natalizumab and MLN-02, but also reviewing other potentially promising therapies targeted towards other mechanisms of action (table 1).

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    Table 1

     Biotechnology compounds that have been or are being evaluated for the treatment of patients with inflammatory bowel disease

    INHIBITION OF TNF

    Comparative mechanisms of action for various anti-TNF agents

    TNF is elevated in the mucosa of patients with CD,1 and inhibition of TNF has been an effective treatment strategy.2 Comparison of various anti-TNF agents with respect to biologic construction, ability to bind soluble and membrane bound TNF, ability to fix complement, ability to mediate antibody dependent cytotoxicity, ability to cause T cell apoptosis, and efficacy in unselected patients versus efficacy primarily in patients with elevated concentrations of C reactive protein (CRP) is shown in table 2. The efficacy of the anti-TNF agent infliximab in unselected patients with …

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