Pre-treatment affinity for LJP 394 influences pharmacodynamic response in lupus patients

Five prospective clinical studies in lupus patients have shown that LJP 394 can reduce circulating anti-dsDNA antibody levels without causing generali zed immunosuppression. The compound is currently being evaluated in a phase III clinical trial for the prevention of renal flares in patients with hig h-affinity antibodies to LJP 394 and a history of lupus nephritis. The curr ent study analyzed the affinity of patient IgG for LJP 394 prior to and fol lowing 4 months of treatment with LJP 394 to determine if pretreatment affi nity influenced pharmacodynamic response. Patient serum samples from a mult icenter, 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 th e 10 mg/week and 50 mg/week groups (P < 0.05 and P < 0.01, respectively), w hereas the placebo group was unchanged. This study demonstrates that weekly treatment with LJP 394 produces a dose-dependent reduction in titer-weight ed average affinity. These results suggest it may be possible to use an aff inity assay to define prospectively patients that are most likely to exhibi t the desired pharmacodynamic response to LJP 394.