REDUCTION IN CIRCULATING dsDNA ANTIBODY TITER AFTER ADMINISTRATION OF LJP 394.

Michael H. Weisman, Harry G. Bluestein, Cecile M. Berner, and Hans A. de Haan.

From the Division of Rheumatic Diseases, School of Medicine, University of California, San Diego, USA.

Supported in part by a grant from La Jolla Pharmaceutical Company, San Diego, CA.

M.H. Weisman, MD, Professor of Medicine; H.G. Bluestein, MD, Professor of Medicine, Division of Rheumatic Diseases, School of Medicine, University of California, San Diego; C.M. Berner, DVM, Associate Director, Clinical Research; H.A. de Haan, MB, FRCS, FFPM, Vice President, Clinical and Regulatory Affairs, La Jolla Pharmaceutical Company, San Diego, CA.

Objective. To examine the safety and immunological effects, in patients with systemic lupus erythematosus (SLE), of LJP 394, a novel B cell toleragen designed to lower dsDNA antibodies.

Methods. Four women with stable SLE were given a 100 mg infusion of LJP 394 and were followed for 4 weeks. Routine safety variables were measured, as well as anti-dsDNA, circulating immune complexes, complement, and complement split products.

Results. Anti-dsDNA titers were promptly lowered. At 4 weeks postinfusion, 2 patients' titers remained below baseline and 2 returned to pretreatment levels. Transient increases in some complement split products were noted; however, no adverse clinical events occurred during or immediately after infusion.

Conclusion. LJP 394 successfully and safely lowered anti-dsDNA in 4 patients with SLE. Immune complex formation and rapid elimination is the most likely explanation for the observed findings.

Published in The Journal of Rheumatology 1997; 24:2.