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Effect of PF-00547659 on Central Nervous System Immune Surveillance and Circulating β7+ T Cells in Crohn's Disease: Report of the TOSCA Study: MADCAM-1Antibody and CNS Immune Surveillance
Journal Contribution - Journal Article
Progressive multifocal leukoencephalopathy, a brain infection associated with anti-integrin drugs that inhibit lymphocyte translocation from bloodstream to tissue, can be fatal. Decreased central-nervous-system immune surveillance leading to this infection has been reported in patients with multiple sclerosis or Crohn's disease treated with anti-integrin antibody natalizumab. PF-00547659 is an investigational human monoclonal antibody for inflammatory bowel disease targeted against α4β7-mucosal addressin cell-adhesion molecule-1 (the integrin ligand selectively expressed in the gut). We hypothesized that this selective agent would not affect central-nervous-system immune surveillance. Cerebral spinal fluid from five healthy volunteers and 10 patients with Crohn's disease previously treated with immunosuppressants was evaluated to assess the feasibility of the study. Subsequently, 39 patients with active Crohn's disease and prior immunosuppression were evaluated over 12 weeks of PF-00547659-induction therapy. We measured total lymphocytes, T-cell subsets in cerebral spinal fluid, and circulating β7 + memory cells. Disease activity was assessed using the Harvey-Bradshaw Index.
Journal: Journal of Crohn's and Colitis
Pages: 188 - 196