EFFECT OF LJP 394, HIGH DOSE CORTICOSTEROIDS AND CYCLOPHOSPHAMIDE (HDCC) 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 reduces anti-dsDNA B cells and circulating anti-dsDNA antibodies. A double-blind, placebo-controlled trial showed that LJP 394 increased time to renal flare and time to HDCC in patients whose antibodies had high affinity for the LJP 394 dsDNA epitope.

Objective: To evaluate the effect of LJP 394 and HDCC on circulating anti-dsDNA antibodies in SLE patients.

Methods: 230 SLE patients with a history of renal disease and anti-dsDNA antibodies = 15 IU/ml were randomized to receive weekly infusions of 100 mg LJP 394 or PBO for 16 weeks, followed by intermittent dosing with 50 mg LJP 394 or PBO for 60 weeks. HDCC was defined as systemic prednisone or equivalent > 200 mg/day or increased = 15 mg per day to > 20 mg per day for more than 2 days, or any exposure to cyclophosphamide.

Results: 62 patients required HDCC (23 LJP 394, 39 placebo). 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 were 76 ± 33 (-38 ± 9%) and 116 ± 25 IU/ml (-23 ± 5%) for LJP 394 and placebo, respectively. By comparison, 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.

Conclusion: Weekly treatment with 100 mg LJP 394 selectively reduces anti-dsDNA antibody levels in SLE patients. The magnitude of this reduction was similar to that observed within one month following treatment with HDCC.