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INFLAMMATION AND IMMUNOPHARMACOLOGY

Formation, Distribution, and Elimination of Infliximab and Anti-Infliximab Immune Complexes in Cynomolgus Monkeys

Centocor, Inc., Radnor, Pennsylvania (J.R.R., T.J.R., J.V., H.J., M.A.G., C.L.W.); University of Virginia Health Sciences Center, Charlottesville, Virginia (R.P.T.); Charles River Laboratories, Worcester, Massachusetts (M.R.C., S.D.R.); and Department of Pathology, University Hospital, Katholieke Universiteit Leuven, Leuven, Belgium (K.G.)

Infliximab (IFX) is a chimeric IgG1 monoclonal antibody specific for human tumor necrosis factor- that is approved in the United States and Europe for the treatment of rheumatoid arthritis (RA) and Crohn's disease (CD). Approximately 10% of RA and CD patients receiving maintenance treatment with IFX will develop antibodies to IFX. The objective of this study was to develop a model to assess the in vivo formation, distribution, and elimination of immune complexes resulting from a low-level immune response in the presence of the excess concentration of a therapeutic antigen. In this model, cynomolgus monkeys were treated with a single intravenous injection of IFX, followed by injection of either radiolabeled, purified monkey anti-IFX IgG antibody (n = 3, test group) or radiolabeled monkey, nonimmune IgG (n = 3, control group). High-performance liquid chromatography analysis of collected sera revealed a rapid formation of immune complexes comprised of IFX and radiolabeled anti-IFX IgG antibody immune complexes. The terminal half-life of the anti-IFX IgG antibody immune complex was approximately 38 h compared with 86 h for the nonimmune antibody. However, the pharmacokinetic profile of IFX, although slightly lower in concentration over time for the test group, was not notably different relative to the control group. There were no macroscopic or microscopic histological findings in either treatment group. These data confirm that immune complexes between IFX and anti-IFX IgG antibodies can form in vivo and that these immune complexes are eliminated more rapidly than nonimmune antibodies in the presence of excess IFX.

Address correspondence to: Jeannie R. Rojas, Centocor, Inc., 145 King of Prussia Road, Radnor, PA 19087. E-mail: jrojas{at}cntus.jnj.com

This article has been cited by other articles:

				C J van der Laken, A E Voskuyl, J C Roos, M Stigter van Walsum, E R de Groot, G Wolbink, B A C Dijkmans, and L A Aarden Imaging and serum analysis of immune complex formation of radiolabelled infliximab and anti-infliximab in responders and non-responders to therapy for rheumatoid arthritis Ann Rheum Dis, February 1, 2007; 66(2): 253 - 256. [Abstract] [Full Text] [PDF]