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Investigational therapies in the medical management of Crohn disease

Author
Joshua R Korzenik, MD
Section Editor
Paul Rutgeerts, MD, PhD, FRCP
Deputy Editor
Shilpa Grover, MD, MPH

INTRODUCTION

Crohn disease is the focus of unprecedented interest for new potential therapeutics. Since the approval of infliximab for the treatment of Crohn disease in 1998, Crohn disease has been viewed as an excellent proving ground for anti-inflammatory biologics.

Despite increasing available therapies, the approved therapies have limited efficacy, and there continues to be concern related to their safety. Thus, a large unmet need exists for the treatment of Crohn disease. Mesalamine, though used widely in Crohn disease, has a minor role with little data supportive of a significant benefit, if any, for the treatment of Crohn disease. Glucocorticoids, while clinically useful, do not completely control the disease in many patients and have no role for maintenance. While some patients respond to the available anti-tumor necrosis factor (TNF) agent, many fail to respond or lose response over time. Thus, newer approaches are being evaluated.

The dramatic advances in mucosal immunology have revealed a broad set of new targets to resolve the inflammation and symptoms of the disease. The prevailing understanding of Crohn disease suggests that the intestinal inflammation is initiated by an aberrant innate immune response, which eventuates in a T-cell driven process, characterized by a T-helper cell 1 type cytokine profile. Many new treatments focus on inhibiting, suppressing, or altering T-cell differentiation. With the identification of a T-cell subset, Th17, which may be responsible for much of the inflammatory process and production of inflammatory cytokines, a new set of therapeutic antibodies are in early phase of testing. The importance of Treg (a T-cell subset that regulates other T cells) has also opened other potential avenues for influencing activated T cells such as targeting SMAD7. (See "Normal B and T lymphocyte development", section on 'Th17 cells'.)

In addition to efforts to manipulate T cells, T-cell products, or inflammatory pathways, other therapeutics are being investigated that take very different theoretical approaches. Examples include the administration or cytokines to stimulate innate immunity, or the use of prebiotics, complex carbohydrates to alter the gut flora. With the approval of vedolizumab, the approach of selective adhesion molecule antagonist is also a focus of considerable effort for new therapies for Crohn disease.

This topic review will discuss experimental treatments for Crohn disease. None of the treatments that will be discussed is currently approved for routine clinical application. Furthermore, because many of these agents are in early stages of development, information regarding their efficacy and safety is derived largely from unpublished sources of data.

                                          

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Literature review current through: Nov 2016. | This topic last updated: Thu Aug 25 00:00:00 GMT+00:00 2016.
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