McNeeley PA1, Iverson GM1, Furie RA2, Cash JM3, Cronin ME4, Katz RS5, Weisman MH6, Aranow C7, Linnik MD1.

1. La Jolla Pharmaceutical Company, San Diego, CA
2. North Shore University Hospital, NYU School of Medicine, Manhasset, NY
3. The Cleveland Clinic Foundation, Cleveland, OH
4. Medical College of WI, Milwaukee, WI
5. Rheumatology Associates, Chicago, IL
6. Cedars-Sinai Medical Center, Los Angeles, CA
7. State University of New York-downstate, Brooklyn, NY.

Five prospective clinical studies in lupus patients have shown that LJP 394 can reduce circulating anti-dsDNA antibody levels without causing generalized immunosuppression. The compound is currently being evaluated in a phase III clinical trial for the prevention of renal flares in patients with high-affinity antibodies to LJP 394 and a history of lupus nephritis. The current study analyzed the affinity of patient IgG for LJP 394 prior to and following 4 months of treatment with LJP 394 to determine if pretreatment affinity influenced pharmacodynamic response. Patient serum samples from a multicenter, double-blind, placebo-controlled trial were evaluated prior to and following 4 months of weekly, biweekly or monthly treatment with placebo (n = 9) or weekly treatment with 10 mg LJP 394 (n = 6) or 50 mg LJP 394 (n = 4). After treatment there was a dose-dependent reduction in affinity in the 10 mg/week and 50 mg/week groups (P < 0.05 and P < 0.01, respectively), whereas the placebo group was unchanged. This study demonstrates that weekly treatment with LJP 394 produces a dose-dependent reduction in titer-weighted average affinity. These results suggest it may be possible to use an affinity assay to define prospectively patients that are most likely to exhibit the desired pharmacodynamic response to LJP 394.

Published in Lupus, 2001;10: 526-532.