Journal
PLOS ONE
Volume 8, Issue 3, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0058438
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Funding
- UCB Pharma
- Biogen Idec Inc.
- Infusion Communications
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Background: Lymphocyte inhibition by antagonism of alpha 4 integrins is a validated therapeutic approach for relapsing multiple sclerosis (RMS). Objective: Investigate the effect of CDP323, an oral alpha(4)-integrin inhibitor, on lymphocyte biomarkers in RMS. Methods: Seventy-one RMS subjects aged 18-65 years with Expanded Disability Status Scale scores <= 6.5 were randomized to 28-day treatment with CDP323 100 mg twice daily (bid), 500 mg bid, 1000 mg once daily (qd), 1000 mg bid, or placebo. Results: Relative to placebo, all dosages of CDP323 significantly decreased the capacity of lymphocytes to bind vascular adhesion molecule-1 (VCAM-1) and the expression of alpha(4)-integrin on VCAM-1-binding cells. All but the 100-mg bid dosage significantly increased total lymphocytes and naive B cells, memory B cells, and T cells in peripheral blood compared with placebo, and the dose-response relationship was shown to be linear. Marked increases were also observed in natural killer cells and hematopoietic progenitor cells, but only with the 500-mg bid and 1000-mg bid dosages. There were no significant changes in monocytes. The number of samples for regulator and inflammatory T cells was too small to draw any definitive conclusions. Conclusions: CDP323 at daily doses of 1000 or 2000 mg induced significant increases in total lymphocyte count and suppressed VCAM-1 binding by reducing unbound very late antigen-4 expression on lymphocytes.
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