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EFFICACY RESULTS FROM A RCT OF LJP 394 IN SLE PATIENTS WITH HISTORY
OF RENAL DISEASE
James A Tumlin, MD1 , C Hura MD2 and G Appel
MD3
1 Renal Division, Emory University, Atlanta, GA, United
States
2 Research Division, San Antonio Kidney Disease Ctr.,
San Antonio, TX, United States
3 Director Clinical Nephrology, Columbia-Presbyterian
Medical Center, New York, NY, United States
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 >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 baseline anti-dsDNA showed high affinity for the LJP 394
epitope (145 LJP 394; 153 PBO). RF's were defined by 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 both 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 to 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. Overall incidence
of adverse events and serious adverse events were comparable in
both 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
Presented at the
36th Annual Meeting of the American Society of Nephrology
San Diego, CA
November 12-17, 2003
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