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Biologic Therapy of Ulcerative Colitis: Natalizumab, Vedolizumab, Etrolizumab (rhuMAb β7)

  • Julián Panés
  • Daniel Benítez-Ribas
  • Azucena Salas
Chapter

Abstract

Recruitment of circulating leukocytes to areas of inflammation is a key process in the pathophysiology of inflammatory bowel diseases. This is a finely regulated multistep process in which specialized adhesion and signaling molecules mediate a series of sequential steps governed by different sets of molecular determinants. Following activation, integrins expressed on the surface of leukocytes are the key mediators of firm adhesion and emigration through interaction with immunoglobulin superfamily molecules expressed on the endothelium. Selective blockade of the β2-integrin receptor ICAM-1 was not effective for treatment of Crohn’s disease. The anti-α4 antibody natalizumab has shown efficacy for induction and for maintenance of response and remission in patients with moderate and severe Crohn’s disease, but a major safety setback such as the appearance of progressive multifocal leucoencephalopathy in 1/1,000 treated cases led to impose limitations to its clinical use and search for more specific blocking mechanisms. The more selective anti-α4β7 antibody vedolizumab has proved efficacious for induction of clinical and endoscopic remission in ulcerative colitis, and initial results also suggest efficacy for induction of response in Crohn’s disease. Selective expression of the α4β7 receptor MAdCAM-1 in the intestine may avoid the risk of central nervous system infectious complications associated with the nonselective blockade of all α4 integrins. Also rHUMAb β7, a selective blocker of the β7 subunit expressed in α4β7 and αEβ7 integrins, may be associated with lower risk of infectious complications, but no clinical data on efficacy are available yet for this molecule. In conclusion, the development of safe and effective drugs that target these molecular components of the inflammatory response may yield novel, improved therapies for IBD that cover unmet needs.

Keywords

Adhesion molecules Inflammatory bowel disease Crohn’s disease Ulcerative ­colitis Integrins Natalizumab Vedolizumab 

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Julián Panés
    • 1
    • 2
  • Daniel Benítez-Ribas
    • 3
  • Azucena Salas
    • 2
    • 4
  1. 1.Department of GastroenterologyHospital Clínic Barcelona, CIBERehd Instituto Salud Carlos IIIBarcelonaSpain
  2. 2.Department of GastroenterologyHospital Clínic de BarcelonaBarcelonaSpain
  3. 3.Department of GastroenterologyCIBERehdBarcelonaSpain
  4. 4.Institut Investigacions Biomètiques August Pi Sunyer (IDIBAPS)BarcelonaSpain

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