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RENAL FLARE IN SLE PATIENTS WITH IMPAIRED RENAL FUNCTION IN A
RCT OF LJP 394
James A Tumlin, MD2, M H Cardiel, MD3, R
A Furie, MD4, D J Wallace, MD5 and C Hura
MD1
1 Research Center, San Antonio Kidney Disease Center,
San Antonio, TX, United States
2 Renal Division, Emory University, Atlanta, GA, United
States
3 Depto de Immunology y Rheumatology, Instituto Nacional
de Ciencas Medicas y Nutricion Salvador Zubiran, Mexico City,
CP, Mexico
4 Rheumatology, North Shore University Hospital, Manhasset,
NY, United States
5 Wallace Rheumatic Study Center, Los Angeles, CA,
United States .
Purpose:
To determine if LJP 394 delays or prevents renal flares (RF's)
in patients (pts) with impaired renal function (IRF) in SLE pts
with a hx of renal disease (RD).
LJP 394 is an immunomodulatory agent designed to delay SLE RD
and prevent RF's by selectively inducing B cell tolerance in anti-dsDNA
B cells and reducing circulating levels of anti-dsDNA antibodies
(abs). In a prior phase 2/3 study of LJP 394 approximately 90%
of pts had high affinity (HA) abs to LJP 394 at baseline. Of these
189 pts, LJP 394 treated pts experienced significantly longer
time to RF and fewer RF's when compared to placebo (PBO). Twenty-two
of these 189 pts had IRF at baseline, defined as serum creatinine
(SrCr) > 1.5 mg/dl. Six of these 22 pts experienced
a RF: 0/11 LJP 394 and 6/11 (55%) PBO. The phase 3 study evaluated
this preliminary finding. In a RCT, pts with elevated levels of
anti-dsDNA (Farr assay >15 IU/ml) were randomized to
wkly doses of 100 mg LJP 394 or PBO for up to 22 mths. 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). Pts with IRF were defined as those with SrCr of >1.5mg/dl
at baseline. RF's were defined by reproducible increases in SrCr,
proteinuria and/or hematuria.
There were 43 pts enrolled with IRF, 20 (14%) on LJP 394 and 23
(15%) on PBO. There were 8 pts with IRF that experienced a RF,
2/20 (10%) on LJP 394 and 6/23 (26%) on placebo. In the ITT population
there were fewer RF's in the LJP group (17/145; 12% LJP: 24/153;
16% PBO); this result was not statistically significant (ss).
Incidence of RF in pts with high affinity antibodies to LJP 394
with Baseline SrCr >1.5 mg/dl
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RF Incidence
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Treatment
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Phase 3N (%)
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Phase 2/3N (%)
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LJP 394
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2/20 (10%)
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0/11
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PBO
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6/23 (26%)
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6/11 (55%)
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While the number of pts with IRF in these studies was small and
results not ss, it appears that LJP 394 may be of benefit in reducing
RF's in SLE pts with a history of RD who have IRF.
Presented at the
36th Annual Meeting of the American Society of Nephrology
San Diego, CA
November 12-17, 2003
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