The clinical trial was funded by Centocor Inc., of which Dr. Woody is an employee. Professor Feldmann is a consultant for Centocor Inc.
Deactivation of vascular endothelium by monoclonal anti–tumor necrosis factor α antibody in rheumatoid arthritis
Article first published online: 12 DEC 2005
Copyright © 1996 American College of Rheumatology
Arthritis & Rheumatism
Volume 39, Issue 7, pages 1082–1091, July 1996
How to Cite
Paleolog, E. M., Hunt, M., Elliott, M. J., Feldmann, M., Maini, R. N. and Woody, J. N. (1996), Deactivation of vascular endothelium by monoclonal anti–tumor necrosis factor α antibody in rheumatoid arthritis. Arthritis & Rheumatism, 39: 1082–1091. doi: 10.1002/art.1780390703
- Issue published online: 12 DEC 2005
- Article first published online: 12 DEC 2005
- Manuscript Accepted: 8 FEB 1996
- Manuscript Received: 15 NOV 1995
- Arthritis and Rheumatism Council of Great Britain
- British Heart Foundation
Objective. To assess whether monoclonal antibody to tumor necrosis factor α (TNFα) reduces endothelial activation in rheumatoid arthritis (RA).
Methods. Levels of serum E-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1), and circulating leukocytes (differential counts) were measured in RA patients before and up to 4 weeks after infusion of either placebo or chimeric anti-TNFα antibody cA2 (1 or 10 mg/kg).
Results. Treatment with anti-TNFα decreased serum E-selectin and ICAM-1 levels, with the earliest detectable changes observed on days 1–3 after anti-TNFα infusion. No effect on VCAM-1 levels was detected. In parallel, there was a rapid and sustained increase in circulating lymphocytes. The extent of the decrease in serum E-selectin and ICAM-1 levels and the increase in lymphocyte counts was significantly higher (P ≤ 0.05) in patients in whom a clinical benefit of anti-TNFα was observed (≥20% response, by Paulus criteria, at week 4) compared with that in patients who failed to respond to anti-TNFα at this time point.
Conclusion. We propose that decreased serum levels of adhesion molecules may reflect diminished activation of endothelial cells in the synovial microvasculature, leading to reduced migration of leukocytes into synovial joints, and thus prolonging the therapeutic effect of anti-TNFα in RA.