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New Insight in Inflammatory Bowel Disease Pathophysiology: Current and Future Therapeutic Applications
Author(s) -
Reimund Jean Marie,
Freund JeanNoël,
Duclos Bernard
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.350.3
Subject(s) - vedolizumab , monoclonal antibody , medicine , ustekinumab , inflammatory bowel disease , immunology , crohn's disease , antibody , ulcerative colitis , natalizumab , tumor necrosis factor alpha , disease , adalimumab , multiple sclerosis
Inflammatory bowel diseases [IBD: Crohn's disease (CD) and ulcerative colitis (UC)] can be difficult to control with conventional treatments (5‐aminosalicylates, corticosteroids and/or immunosuppressors). The advent and the growing use of anti‐TNF‐alpha monoclonal antibodies in IBD represented a remarkable progress in IBD therapy. Nevertheless, not all patients respond to anti‐TNF‐alpha antibodies and others, either present secondary side effects or failure after initial response to these antibodies, and as a consequence the need to stop them. It is now demonstrated that a greater understanding of IBD pathophysiology may conduct to identify new targets for IBD treatment and remains a continuous challenge, potentially allowing the development of active therapeutic molecules. Some of them are currently in phase II or III trials or near to be launched. As an example, basic research led to the development of anti‐interleukin (IL)‐12/23 monoclonal antibodies (ustekinumab, Janssen) or of anti‐integrin monoclonal antibodies in particular anti‐a 4 b 7 integrins antibodies (vedolizumab, Takeda) or anti‐a x b 7 monoclonal antibodies (etrolizumab, Roche Gentech) which block the interactions between leukocytes and the intestinal vascular endothelial cells. In addition, other drugs (small molecules or monoclonal antibodies) will enlarge the therapeutic armamentarium in IBD, blocking or interfering with targets such as Janus kinase (Jak) inhibitors (small molecules designed to block intracellular signaling of several pro‐inflammatory cytokines), stimulation of Toll‐like receptor (TLR)‐9, regulatory T cell therapy, etc. One other future direction will probably include the identification of potential therapeutic targets in intestinal microbiota, an important but difficult research field in IBD. Here, these new approaches will be discussed as well as their current or future place in IBD treatment strategy.