Therapeutic value of alpha-4 integrin blockade in inflammatory bowel disease:the role of natalizumab.
Lymphocyte infiltration into the intestinal tract in Crohn's disease is mediated by the interaction between alpha(4) integrin, expressed on lymphocytes, and its ligand mucosal vascular addressin cell-adhesion molecule-1 (MADCAM-1), expressed on the endothelial cells of the microvasculature in inflamed intestinal tract. Natalizumab, a recombinant, humanised monoclonal antibody against alpha(4) integrin was effective in Crohn's disease in a Phase II, randomised, controlled trial. The highest response rate and remission rates were 71 and 44% at 6 weeks, respectively, after two infusions of 3 mg of natalizumab administered 4 weeks apart. Natalizumab was well-tolerated in this study. The Phase III trial results are awaited.
Ghosh
Subrata
S
Imperial College London, Hammersmith Hospital, Ducane Road, London W12 0NN, UK. s.ghosh@ic.ac.uk
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015815:Cell Adhesion Molecules; D002986:Clinical Trials as Topic; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D039441:Integrin alpha4 / Q000276:immunology*; D009088:Mucoproteins / Q000276:immunology; D000069442:Natalizumab; D016201:Receptors, Lymphocyte Homing / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C504265:MADCAM1 protein, human; D009088:Mucoproteins; D000069442:Natalizumab; D016201:Receptors, Lymphocyte Homing; D039441:Integrin alpha4