REDUCTIONS IN ANTI-DSDNA ANTIBODIES AND REDUCED RISK OF SLE RENAL FLARE AND MAJOR SLE FLARE


Matthew D Linnik, PhD 2, T Joh PhD 2 and J A Tumlin, MD 1

1 Renal Division, Emory University, Atlanta, GA, United States
2 La Jolla Pharmaceutical Company, San Diego, CA, United States

A novel analysis evaluated the potential clinical benefit of maintaining a sustained reduction in anti-dsDNA antibody levels in SLE patients (pts) with a history of renal disease. The objective was to determine if sustained reductions in anti-dsDNA antibody levels reduce the risk of renal flare (RF) or Major SLE flare (MSF). Sustained Reductions in anti-dsDNA antibody levels were defined by a
>10% reduction in anti-dsDNA antibodies from baseline for >2/3 of all observed values using Farr assay. Patients were stratified into one of two groups: 1) Sustained Reduction, if they met the aforementioned criteria or 2) Other, if they failed to meet criteria for sustained reduction. The LJP 394-90-09 (90-09) and LJP 394-90-05 (90-05) clinical trial databases were analyzed as they represent two large studies that examined anti-dsDNA antibodies and renal outcomes in SLE pts. The ITT group in the 90-09 study consisted of 298 pts treated with
LJP 394 (n=145) or placebo (PBO; n=153) for up to 22 months. In the 90-05 study, 189 similar pts (LJP: n=92; PBO: n=97) were treated for up to 18 months. Renal Flares were defined by significant, reproducible changes in serum creatinine, proteinuria and/or hematuria. Major SLE flares were defined by treatment with high dose corticosteroids or immunosuppressive drugs or hospitalization or death due to SLE.
Results as follows:


Conclusion: SLE pts with sustained reductions in anti-dsDNA abs had a lower incidence of renal flare and Major SLE flare. Of the 41 RF in 90-09, 5 (12%) occurred in the sustained reduction group, whereas 36 (88%) occurred in the other group. Of the 28 RF in 90-05, 2 (7%) occurred in the sustained reduction group, and 26 (93%) occurred in the other group. The reduced risk of renal flare or Major SLE flare in pts with sustained reductions in anti-dsDNA antibodies was independent of treatment assignment. Treatment with LJP 394 resulted in two- (80:41, LJP 394:PBO) to four-fold (54:13, LJP 394:PBO) greater numbers of pts with sustained reductions in anti-dsDNA antibodies in the two trials.

Presented at the
36th Annual Meeting of the American Society of Nephrology
San Diego, CA
November 12-17, 2003