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CLINICAL EFFICACY RESULTS FROM A RCT OF LJP 394 IN SLE PATIENTS
WITH HISTORY OF RENAL DISEASE
Mario H Cardiel, James A Tumlin, Richard A Furie, Daniel J Wallace,
Claudia Hura, Vibeke Strand, Toni Foster, Jay Hu, Kenneth R Heilbrunn,
Matthew D Linnik
Purpose:
Determine if LJP 394 delays or prevents renal flares (RF), treatment
with high-dose corticosteroids and/or cyclophosphamide (HDCC),
or Major SLE flare (MSF) and to determine if LJP 394 reduces anti-dsDNA
antibody (anti-dsDNA) levels in SLE patients (pts) with a history
of renal disease.
Methods:
In a RCT, pts with elevated levels of anti-dsDNA (Farr assay >
15 IU/ml) were randomized to weekly doses of 100 mg LJP 394 or
placebo (PBO) for up to 22 months. The ITT population consisted
of pts whose anti-dsDNA at baseline were shown to have high affinity
for the LJP 394 epitope (145 LJP 394; 153 PBO). RF’s were
defined by significant, reproducible increases in serum creatinine,
proteinuria and/or hematuria. MSF’s were defined by treatment
with HDCC or immunosuppressive agents (IA) or hospitalization
or death due to SLE.
Results:
Baseline characteristics were similar in the two groups. The mean
duration in the study was 310 days for LJP 394 pts and 341 days
for PBO pts. There were fewer RF’s (17/145; 12% LJP: 24/153;
16% PBO) and fewer MSF’s (35/145; 24% LJP: 47/153; 31% PBO)
in LJP 394 pts, although these differences were not statistically
significant. The incidence of HDCC (33/145; 23% LJP: 36/153; 24%
PBO) was similar in the two groups. The estimated median time
to RF was 123 months in the LJP 394 group and 89 months in the
PBO group. The estimated median time to MSF was 55 months in the
LJP 394 group and 42 months in the PBO group.
Treatment with LJP 394 was associated with a statistically significant
reduction in anti-dsDNA from baseline compared with PBO (p<0.0001).
Reductions in anti-dsDNA correlated with increases in C3 (p<0.0001).
Because of the morbidity and mortality associated with renal flares,
study pts were allowed to receive concomitant medications, including
IA’s. In the LJP 394 and PBO groups, 48% and 42% of pts respectively
were on at least one IA, exclusive of prednisone, at baseline.
In both groups, 83% of pts were on prednisone at baseline.
Overall incidence of adverse events and serious adverse events
were comparable between the two groups.
Conclusions:
Treatment with LJP 394 resulted in a 25% lower
incidence of RF’s and a 21% lower incidence of MSF’s
compared to PBO; results were not statistically significant. Treatment
with LJP 394 resulted in a statistically significant lowering
of anti-dsDNA. Anti-dsDNA changes correlated inversely with C3.
The ability of the study to discern the potential clinical benefit
of LJP 394 may have been limited by an increased use of IA’s
compared with the previous phase 2/3 study. Administration of
LJP 394 for periods of up to 22 months appeared to be well tolerated.
Presented at the
67th Annual Meeting of the American College of Rheumatology
Orlando, FL
October 23-28, 2003
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