PROGRESSIVE REDUCTION IN RISK OF RENAL FLARE IN SLE PATIENTS IS ASSOCIATED WITH IMPROVED LONG-TERM CONTROL OF ANTI-DSDNA ANTIBODY LEVELS

Matthew D. Linnik, Tenshang Joh

Abstract

Purpose. Data from two randomized controlled trials (RCT) in SLE patients with elevated anti-dsDNA antibody levels has demonstrated that patients with sustained reductions in anti-dsDNA antibody levels have significantly fewer renal flares than patients with stable or increasing antibody levels. The purpose of the current analysis was to evaluate the importance of the durability of control of anti-dsDNA antibody levels over time as it relates to the risk of renal flare in SLE patients with a history of renal flare.

Methods.These retrospective analyses were based on RCTs LJP 394-90-05 (90-05) and LJP 394-90-09 (90-09). The trials were designed to determine whether treatment with abetimus sodium (LJP 394) delayed time to renal flare. This report includes data from patients with high-affinity antibodies for the abetimus DNA epitope at baseline, established retrospectively in 90-05 (N=189) and prospectively in 90-09 (N=298). Anti-dsDNA antibody levels were centrally measured at least once per month by Farr assay. Renal flares required clinically significant, reproducible increases in serum creatinine, proteinuria and/or hematuria and attribution to SLE assessed by the PI and medical monitor. The responder analysis identifies patients with sustained reductions in anti-dsDNA antibody levels over the duration of the trial. Responders were defined by the durability of response ( >50%, >67%, >75% of all observed values) at a specified level of reduction from baseline (any, >10%, >20%, >30%) in anti-dsDNA antibody levels. Anti-dsDNA antibody values subsequent to initiation of high-dose corticosteroids and/or cyclophosphamide were considered treatment failures and were imputed to have a status greater than baseline.

Results.The frequency of responders at the minimal responder definition
(>50% of total anti-dsDNA antibody values below baseline) was 110/189 (58.2%) and 181/298 (60.7%) in the 90-05 and 90-09 trials. The median % reduction in anti-dsDNA antibody levels for the minimal responder population was 30-40% below baseline and well below the minimal responder requirement. The frequency of renal flare was lower in the minimal responders (5.5% and 5.5%) than in non-responders (27.8% and 26.5%) for 90-05 and 90-09, respectively (p<0.0001). Increasing the criteria for durability of response over time from >50% to >67% to >75% of all anti-dsDNA antibody values below baseline resulted in a progressive reduction in risk of renal flare as the criteria became more stringent.

Conclusion. These results demonstrate that reductions in anti-dsDNA antibody levels are associated with a reduced risk of renal flare in SLE patients with a history of renal disease. A positive relationship was observed between the degree of control in anti-dsDNA antibody levels over time and the risk of renal flare. The results indicate that SLE patients with sustained reductions in anti-dsDNA antibody levels are more likely to have a favorable clinical prognosis than patients with stable or increasing anti-dsDNA antibody levels.

Presented at the
ACR/ARHP Annual Scientific Meeting
November 13-17, 2005