EFFECT OF LJP 394 OR HIGH DOSE CORTICOSTEROIDS AND CYCLOPHOSPHAMIDE ON ANTI-dsDNA ANTIBODIES IN SLE PATIENTS

MD Linnik1, RG Bagin1, V Strand2 and LJP 394-90-05 Investigator Consortium. 1, San Diego, CA; and 2, Palo Alto, CA

Introduction: LJP 394 is a novel B cell toleragen that has been shown to specifically reduce anti-dsDNA B cells in animals and circulating anti-dsDNA antibodies in SLE patients in 6 clinical trials. A double-blind, placebo-controlled trial (90-05 trial) showed that LJP 394 reduced time to renal flare and time to treatment with high dose corticosteroids and/or cyclophosphamide (HDCC) in patients with anti-dsDNA antibodies that have high-affinity binding to the LJP 394 dsDNA epitope.

Objective: To compare the effect of LJP 394 or HDCC administration in decreasing circulating anti-dsDNA antibodies in patients with a history of SLE renal disease.

Methods: In the 90-05 trial, 230 SLE patients with a history of renal disease and anti-dsDNA antibodies > 15 IU/ml by Farr assay were randomized to receive 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. HDCC was administered at the investigator's discretion and 1st exposure in a patient was defined as any exposure to cyclophosphamide or systemic prednisone (or prednisone equivalent) when increased > 15 mg per day over baseline to > 20 mg per day for more than 2 days, or when the daily predisone dose exceeded 200 mg.

Results: LJP 394 reduced anti-dsDNA levels from 100 + 15 IU/ml at baseline to 68 + 12 IU/ml (25 + 3% reduction) after 4 weekly treatments. In patients receiving placebo, levels increased from 106 + 16 IU/ml at baseline to 118 + 19 IU/ml (11 + 5% increase) at 4 weeks, representing a difference in anti-dsDNA of 36% between LJP 394 and placebo. Sixty two patients required HDCC (23 LJP 394 and 39 placebo) and 58/62 had at least one anti-dsDNA determination after the initial dose of HDCC. Mean and median dose of prednisone in the HDCC group were 151 + 42 mg/day and 50 mg/day, respectively. Mean anti-dsDNA levels prior to receiving HDCC were 163 + 47 IU/ml and 178 + 43 IU/ml in LJP 394 and placebo groups, respectively. The lowest anti-dsDNA levels within 4 weeks of HDCC treatment were 76 + 33 and 116 + 25 IU/ml for LJP 394 and placebo, respectively, representing decreases of 38 + 9% and 23 + 5% for LJP 394 and placebo, respectively.

Conclusion: Weekly treatment with 100 mg LJP 394 effectively reduces anti-dsDNA antibody levels with no other known effects on the immune system. The magnitude of this reduction was similar to that observed within one month following treatment with high dose corticosteroids and/or cyclophosphamide.

Presented at
The 65th Annual Scientific Meeting of the American College of Rheumatology
San Francisco, CA., Nov. 11-15, 2001.