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Vedolizumab for the treatment of inflammatory bowel disease.

Abstract
The causes of inflammatory bowel diseases, such as ulcerative colitis (UC) and Crohn's disease (CD), remain to be elucidated. However, characteristic inflammation of the gastrointestinal mucosa is caused by infiltration of T lymphocytes into the submucosal layer. Inhibiting this immune response is a promising therapeutic target. Integrins expressed on the cell surface mediate gut homing of T lymphocytes. Blockade of integrin-cell adhesion molecule interaction using antibodies against α₄-containing integrins, namely natalizumab, has shown clinical efficacy; however, this drug's lack of α₄-containing integrin specificity leads to systemic immunosuppression that caused progressive multifocal leukoencephalopathy and death in some patients resulting in its withdrawal from the market. Vedolizumab specifically targets the α₄β₇ integrin that is selectively expressed on gut-homing T lymphocytes. Vedolizumab successfully extended clinical remission in patients with UC or CD and reduced patient reliance on corticosteroid use. The drug is well tolerated and there have been no deaths or reports of progressive multifocal leukoencephalopathy infection in patients receiving vedolizumab. A phase III long-term 7-year safety study in patients with UC and CD is under way. Regulatory applications are under review in the U.S. and E.U. for its use in the treatment of patients with UC and CD, with decisions expected in mid-2014.
AuthorsK Haddley
JournalDrugs of today (Barcelona, Spain : 1998) (Drugs Today (Barc)) Vol. 50 Issue 4 Pg. 309-19 (Apr 2014) ISSN: 1699-3993 [Print] Spain
PMID24918648 (Publication Type: Journal Article, Review)
CopyrightCopyright 2014 Prous Science, S.A.U. or its licensors. All rights reserved.
Chemical References
  • Antibodies, Monoclonal, Humanized
  • Integrins
  • integrin alpha4beta7
  • vedolizumab
Topics
  • Animals
  • Antibodies, Monoclonal, Humanized (adverse effects, metabolism, therapeutic use)
  • Clinical Trials as Topic
  • Humans
  • Inflammatory Bowel Diseases (drug therapy)
  • Integrins (antagonists & inhibitors)

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