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Mechanisms of Action of Antitumor Necrosis Factor Agents in Crohns Disease

Peake, Simon T. C. MRCP*,†; Bernardo, David PhD*; Mann, Elizabeth R. PhD*; Al-Hassi, Hafid O. PhD*; Knight, Stella C. PhD*; Hart, Ailsa L. PhD*,†

Inflammatory Bowel Diseases:
doi: 10.1097/MIB.0b013e318281333b
Basic Science Review Article
Abstract

Abstract: Crohn’s disease (CD) is characterized by inflammation that can affect any part of the gastrointestinal tract. It is a chronic destructive condition that follows a relapsing–remitting course and can lead to disability and a poor quality of life. Lifelong pharmacotherapy with systemic immunomodulator therapies remains the cornerstone of CD management. Advances in understanding of the immunopathogenic mechanisms underlying chronic gut inflammation in CD have led to the development of effective biological therapies for patients with CD. Tumor necrosis factor α (TNF-α) is a potent proinflammatory cytokine that plays a pivotal role in the development of Crohn’s inflammation. Therapies designed to target this cytokine have revolutionized treatment of CD since their introduction in the late 1990s, thanks to their ability to induce and maintain remission, heal mucosa, reduce hospital admissions and surgical procedures, and restore quality of life. Despite widespread use of these therapies in CD, their precise mechanism of action remains unclear, although several different mechanisms have been proposed. This review summarizes the biology of the TNF-α cytokine and the development of biological therapies targeting TNF-α, and updates our current understanding of mechanisms of action of the commercially available anti-TNF-α therapies used in the treatment of CD.

In Brief

Article first published online 16 April 2013

Author Information

*Antigen Presentation Research Group, Imperial College, Northwick Park and St Mark’s Hospital Campus, Watford Road, Harrow, Middlesex, United Kingdom; and

Inflammatory Bowel Disease Unit, St Mark’s Hospital, Watford Road, Harrow, Middlesex, United Kingdom.

Reprints: Simon T. C. Peake, MRCP, Clinical Research Fellow in Inflammatory Bowel Disease Antigen Presentation Research Group Imperial College London, 7th Floor, St Mark’s Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, United Kingdom (e-mail: s_peake@doctors.org.uk)

The authors have no conflicts of interest to disclose.

Received September 05, 2012

Accepted September 18, 2012

© Crohn's & Colitis Foundation of America, Inc.

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