Natalizumab: a promising treatment for Crohn’s disease

Abstract

A primary feature contributing to the pathology of Crohn’s disease (CD) is inappropriate and persistent recruitment and migration of circulating leukocytes from the bloodstream to affected tissues and organs. These processes are mediated by interactions between α₄ integrin adhesion molecules expressed on leukocyte surfaces and cognate receptors on vascular endothelial cells. Natalizumab is a humanized immunoglobulin G₄ monoclonal antibody against α₄ integrins. Natalizumab has demonstrated efficacy in inducing and maintaining sustained remission in patients with moderately to severely active CD, including those intolerant of or unresponsive to infliximab. Maintenance therapy with natalizumab in adult patients allowed elimination of steroids in a significant number of patients and sustained patients’ quality of life. Natalizumab has been well tolerated in the majority of patients. However, progressive multifocal leukoencephalopathy, a rare opportunistic infection associated with the JC polyomavirus, occurred in three natalizumab-treated patients; two multiple sclerosis patients and one CD patient. This article reviews the properties of natalizumab and addresses its potential benefits and risks in the treatment of CD.

Keywords::

• biologic therapy
• Crohn’s disease
• leukocyte trafficking
• natalizumab
• remission
• steroid sparing

Acknowledgements

Professor Colombel would like to thank Drs Jeffrey Bornstein (Elan Pharmaceuticals, Inc.) and Pauline Carrico (Fission Communications, NY, USA) for their medical and editorial review of this article.