REDUCTION IN ANTIBODIES TO dsDNA USING
LJP 394 IN DOSE RANGING TRIAL IN LUPUS
PATIENTS
MD Linnik(1), M Cardiel(2), ME Cronin(3),
KC Kalunian(4) and N Rothfield(5).
(1)La Jolla Pharmaceutical
Company, San Diego, CA (2)Mexico
City, Mexico (3) Milwaukee, WI (4) Los
Angeles, CA (5) Farmington, CT.
Introduction: LJP 394 is an
antigen-specific B cell toleragen that
decreases anti-dsDNA antibody production.
LJP 394 has been shown to reduce renal
flares and treatments with high dose
corticosteroids &/or cyclophosphamide
in patients whose antibodies have high
affinity binding to the LJP 394 dsDNA
epitope.
Objective: This trial was designed
to investigate the pharmacodynamic effect
of weekly IV injections of LJP 394 or
placebo (PBO) on anti-dsDNA antibody
levels.
Methods: In a double-blinded,
PBO-controlled, multicenter trial conducted
at 22 centers, 74 SLE patients with
anti-dsDNA antibodies of > 25 IU/ml
by the Farr assay received weekly injections
of 10, 50, or 100 mg of LJP 394 or PBO
for 12 weeks.
Results: In PBO treated patients,
anti-dsDNA levels increased slowly to
a final level that was 100 ±
65% of baseline. Anti-dsDNA levels in
patients receiving 10 mg or 50 mg increased
after 12 weeks by 53 ± 20% and
10 ± 17%, respectively and were
not significantly different from PBO.
In patients treated with 100 mg LJP
394, anti-dsDNA antibodies decreased
at all time points with a maximum reduction
of 43 ± 6% from baseline, significantly
different from PBO. Seven LJP 394-treated
patients had serious adverse events,
but none were considered related to
LJP 394 treatment.
Conclusion: Weekly intravenous
injections of LJP 394 at 10, 50, or
100 mg for 12 weeks appeared safe and
well tolerated. The 100 mg/week dose
was significantly more effective than
PBO at reducing anti-dsDNA antibody
concentrations.
Presented at the
3rd International Congress on
Autoimmunity
Geneva,
Switzerland
February 20-24, 2002.
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