Donato Alarcón-Segovia 1, James A. Tumlin 2, Richard A. Furie 3, James D. McKay 4, Mario H. Cardiel 1, Vibeke Strand 5 , Robert G. Bagin 6, Matthew D. Linnik 7 *, Bonnie Hepburn 6 , LJP 394 Investigator Consortium§

1. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
2. Emory University School of Medicine, Atlanta, Georgia
3. North Shore University Hospital, Manhasset, New York
4. Tulsa, Oklahoma
5. Stanford University, Palo Alto, California
6. Santarus, Inc., San Diego, California
7. La Jolla Pharmaceutical Company, San Diego, California

Objective: To determine whether LJP 394 delays or prevents renal flare in patients with systemic lupus erythematosus (SLE) and a history of renal disease. Methods: In a 76-week, double-blind, placebo-controlled study, 230 SLE patients were randomized to receive 16 weekly doses of 100 mg of LJP 394 or placebo, followed by alternating 8-week drug holidays and 12 weekly doses of 50 mg of LJP 394 or placebo. An assay measuring the affinity of the serum IgG fraction for the DNA epitope of LJP 394 identified a high-affinity population of patients (189 of 213 patients; 89% taking LJP 394 and 90% taking placebo). Analyses were performed on both the intent-to-treat population and the high-affinity population.

Results: Anti-double-stranded DNA antibodies decreased and C3 levels tended to increase during treatment with LJP 394. In the intent-to-treat population, the time to renal flare was not significantly different between treatment groups, but patients taking LJP 394 had a longer time to institution of high-dose corticosteroids and/or cyclophosphamide (HDCC) and required 41% fewer treatments with HDCC. In the high-affinity population, the LJP 394 group experienced a longer time to renal flare, 67% fewer renal flares, longer time to institution of HDCC, and 62% fewer HDCC treatments compared with the placebo group. In patients with serum creatinine levels 1.5 mg/dl at study entry, those taking LJP 394 had 50% fewer renal flares; no renal flares were observed in the high-affinity group taking LJP 394. Serious adverse events were observed in 25 of the 114 LJP 394-treated patients (21.9%) and 34 of the 116 placebo-treated patients (29.3%).

Conclusion: Treatment with LJP 394 in patients with high-affinity antibodies to its DNA epitope prolonged the time to renal flare, decreased the number of renal flares, and required fewer HDCC treatments compared with placebo. The study drug appeared to be well tolerated.

Published in Arthritis and Rheumatism, 2003, Volume 48, Issue 2: pp 442-454