Inflammatory Bowel Diseases

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

Mechanisms of Action of Anti–tumor Necrosis Factor α Agents in Crohn’s 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*,†

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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.

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

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