THE EFFECT OF LJP 394 AND CONCOMITANT IMMUNOSUPPRESSIVE AGENTS ON LEVELS OF ANTI-DSDNA ANTIBODIES IN SLE PATIENTS

Kenneth R Heilbrunn, MH Cardiel, JA Tumlin, RA Furie, DJ Wallace, C Hura, V Strand, T Joh

Purpose: To determine the effect of LJP 394 and concomitant immunosuppressive agents (IA) on levels of anti-dsDNA antibodies (anti-dsDNA) in SLE patients (pts) with a history of renal disease. LJP 394 is a novel, immunomodulatory agent designed to specifically reduce anti-dsDNA levels.

Methods: Data from a Phase 3 randomized, placebo controlled trial (RCT) were analyzed to assess the treatment effect of LJP 394 and concomitant IA on anti-dsDNA levels. The RCT enrolled 298 pts with high-affinity antibodies to the oligonuceotide epitope of LJP 394 (145 LJP 394; 153 placebo [pbo]) who received weekly treatment for up to 22 months (100 mg LJP 394 or pbo). Pts had SLE, a history of renal disease, and elevated anti-dsDNA levels. anti-dsDNA levels were evaluated at least monthly by Farr assay utilizing a central lab. Changes in anti-dsDNA levels were compared in LJP 394 and pbo treated pts who were receiving either mycophenolate mofetil (MMF) or azathioprine (AZA) at baseline.

Results: 83% of pts in both treatment arms were receiving prednisone at baseline; 48% and 42% of pts were receiving an IA at baseline in the LJP 394 and pbo groups, respectively. 42 pts were receiving MMF at baseline (20 LJP 394 and 22 pbo) and 74 pts were receiving AZA at baseline (38 LJP 394 and 36 pbo). Baseline characteristics were similar between treatment groups.
Treatment with LJP 394 was associated with a statistically significant and persistent decrease in anti-dsDNA levels from baseline compared to pbo treated pts (p< 0.0001). LJP 394 treated pts who were on MMF at baseline experienced a greater decrease in median anti-dsDNA levels compared to pbo pts receiving MMF at baseline. At week 4, LJP 394 treated pts who were on MMF at baseline experienced a median reduction in anti-dsDNA levels of 31% compared to a 1% median reduction for the pbo pts. By week 24, the LJP 394 treated pts experienced a median reduction of 55% compared to a median reduction of 6% for the pbo pts. Similar results were observed for LJP 394 treated pts who were on AZA at baseline compared to pbo pts receiving AZA at baseline. At week 4, LJP 394 treated pts who were on AZA at baseline experienced a median reduction in anti-dsDNA levels of 16% compared to a 3% median increase for the pbo pts. By week 24, the LJP 394 treated pts experienced a median reduction of 28% compared to a median reduction of 1% for the pbo pts.

Conclusion: In a RCT in SLE pts with a history of renal disease, treatment with LJP 394 resulted in significant and persistent reductions in anti-dsDNA levels. Because of the morbidity and mortality associated with renal flares, pts were allowed to receive concomitant medications, including IA. Pts treated with LJP 394 and who were on MMF or AZA at baseline had a greater reduction in anti-dsDNA levels compared to pbo pts on MMF or AZA at baseline.

Presented at the
American College of Rheumatology 68th Annual Scientific Meeting
San Antonio, TX
Oct. 16-21, 2004