Matthew D. Linnik and Robert G. Bagin, La Jolla Pharmaceutical Co., San Diego, CA 92121

Introduction: LJP 394 has been shown to reduce autoantibodies to dsDNA in SLE patients in 5 clinical trials. A double-blind, placebo-controlled trial (90-05 trial) was conducted to determine if LJP 394 reduces time to renal flare in these patients. The objective of this analysis was to assess clinical course of a subgroup of patients from the 90-05 trial with the greatest impairment of renal function at baseline as defined by serum creatinine levels.

Methods: Patients with antibodies to dsDNA and a history of lupus renal disease received weekly infusions of 100 mg LJP 394 or placebo for 16 weeks, followed by intermittent dosing with 50 mg LJP 394 or PBO for 60 weeks. Patients with active renal disease or serum creatinine > 2.5 mg/dl were excluded from the trial. A renal flare was recorded if there was a significant and reproducible increase in serum creatinine, proteinuria or hematuria that was attributed to SLE by the physician. This analysis assessed renal outcome of a subgroup of patients with greatest impairment of renal function at baseline as defined by those patients who entered the trial with serum creatinine > 1.5 mg/dl.

Results: Serum creatinine values > 1.5 mg/dl at study entry were recorded in 16/105 (15%) LJP 394 patients was 10/106 (9%) PBO patients. Baseline serum creatinine in LJP 394 and PBO subgroups was 1.8 + 0.28 and 1.95 + 0.37 mg/dl, respectively (mean + SD). No significant differences in baseline demographics were noted between treatment groups. Nine of the 26 patients (35%) in this subgroup recorded a renal flare during the 90-05 trial compared with 42 of 211 patients (20%) in the entire cohort of patients in the trial. Renal flares were recorded in 3/16 (19%) LJP 394 patients and 6/10 (60%) PBO patients in the subgroup analysis. When patients' pretreatment antibodies were analyzed for affinity to drug, 10/10 placebo patients and 11/16 LJP 394 patients had high-affinity antibodies to drug. No renal flares were observed in the high-affinity, drug-treated subgroup.

Conclusion: LJP 394 may provide clinical benefit to SLE patients with impaired renal function and elevated serum creatinine levels.

Presented at The 64th Annual Scientific Meeting of the American College of Rheumatology, Philadelphia, PA., Oct. 29 - Nov. 2, 2000.