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SLE PATIENTS WITH SUSTAINED REDUCTIONS IN ANTI-DSDNA ANTIBODIES
HAVE A REDUCED RISK OF RENAL FLARE AND MAJOR SLE FLARE
Matthew D Linnik, Tenshang Joh, Vibeke Strand,
Mario H Cardiel, James A Tumlin, Richard A Furie, Daniel J Wallace,
Claudia Hura
A novel analysis evaluated the potential clinical
benefit of maintaining a sustained reduction in anti-dsDNA antibody
levels in SLE patients (pts) with a history of renal disease.
The objective of the assessment was to determine if sustained
reductions in anti-dsDNA antibody levels reduce the risk of renal
flare or Major SLE flare (MSF). Sustained reductions in anti-dsDNA
antibody levels were defined by a >10% reduction in
anti-dsDNA antibodies from baseline for >2/3 of all
observed values using Farr assay. Patients were stratified into
one of two groups: 1) Sustained Reduction, if they
met the aforementioned criteria or 2) Other, if they failed
to meet criteria for sustained reduction.
The LJP 394-90-09 (90-09) and LJP 394-90-05
(90-05) clinical trial databases were analyzed as they represent
two large studies that examined anti-dsDNA antibodies and renal
outcomes in SLE pts. The ITT group in the 90-09 study consisted
of 298 pts treated with LJP 394 (n=145) or placebo (PBO;n=153)
for up to 22 months. In the 90-05 study, 189 similar pts (LJP:
n=92; PBO: n=97) were treated for up to 18 months. Renal flares
were defined by significant, reproducible changes in serum creatinine,
proteinuria and/or hematuria. Major SLE flares were defined by
treatment with high dose corticosteroids or immunosuppressive
drugs or hospitalization or death due to SLE. The results are
as follows:
Renal flare (RF) in Pts with and without
sustained reductions in anti-dsDNA antibodies
|
Trial
|
Rx
|
Sustained Reduction
|
Other
|
Total RF
|
|
Pts
|
RF (%)
|
Pts
|
RF (%)
|
|
90-09
|
PBO
|
41
|
2 (5%)
|
112
|
22 (20%)
|
24
|
|
LJP 394*
|
80
|
3 (4%)
|
65
|
14 (22%)
|
17
|
|
Total†
|
121
|
5 (4%)
|
177
|
36 (20%)
|
41
|
|
90-05
|
PBO
|
13
|
1 (8%)
|
84
|
20 (24%)
|
21
|
|
LJP 394*
|
54
|
1 (2%)
|
38
|
6 (16%)
|
7
|
|
Total††
|
67
|
2 (3%)
|
122
|
26 (21%)
|
28
|
Major SLE flare (MSF) in Pts with and without
sustained reductions in anti-dsDNA antibodies
|
Trial
|
Rx
|
Sustained Reduction
|
Other
|
Total MSF
|
|
Pts
|
MSF (%)
|
Pts
|
MSF (%)
|
|
90-09
|
PBO
|
41
|
4 (10%)
|
112
|
43 (38%)
|
47
|
|
LJP 394*
|
80
|
10 (13%)
|
65
|
25 (38%)
|
35
|
|
Total†
|
121
|
14 (12%)
|
177
|
68 (38%)
|
82
|
|
90-05
|
PBO
|
13
|
3 (23%)
|
84
|
38 (45%)
|
41
|
|
LJP 394*
|
54
|
5 (9%)
|
38
|
17 (45%)
|
22
|
|
Total†
|
67
|
8 (12%)
|
122
|
55 (45%)
|
63
|
*p < 0.0001 by Fisher’s exact
test to determine if LJP 394 treated pts were more likely to have
sustained reductions in anti-dsDNA antibodies than PBO treated
pts
†p < 0.0001(††=
0.0004) by Fisher’s exact test to determine if pts with sustained
reductions in anti-dsDNA antibodies are at reduced risk of renal
flare or Major SLE flare
Conclusions
SLE pts with sustained reductions in anti-dsDNA
antibodies had a lower incidence of renal flare and Major SLE
flare. Of the 41 RF in 90-09, 5 (12%) occurred in the sustained
reduction group, whereas 36 (88%) occurred in the other group.
Of the 28 RF in 90-05, 2 (7%) occurred in the sustained reduction
group, and 26 (93%) occurred in the other group. The reduced risk
of renal flare or Major SLE flare in pts with sustained reductions
in anti-dsDNA antibodies was independent of treatment assignment.
Treatment with LJP 394 resulted in two- (80:41, LJP 394:PBO) to
four-fold (54:13, LJP 394:PBO) greater numbers of pts with sustained
reductions in anti-dsDNA antibodies in the two trials.
Presented at the
67th Annual Meeting of the American College
of Rheumatology
Orlando, FL
October 23-28, 2003
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