SLE TRIAL SHOWS FEWER RENAL FLARES IN LJP 394-TREATED PATIENTS WITH
HIGH-AFFINITY ANTIBODIES TO LJP 394: 90-05 TRIAL RESULTS.
D. Alarcon-Segovia, MD, J Tumlin, MD, R Furie, MD, J McKay, DO,
M Cardiel, MD, M Linnik, PhD, B Hepburn, MD. 1Mexico City. 2Decatur, GA.
3Manhasset, NY. 4Tulsa, OK. 5Mexico City. 6San Diego, CA. 7San Diego, CA.
Introduction: LJP 394 is a molecule with 4 ds-oligonucleotide
strands attached to an inert platform. It binds aDNA in blood and on the
B-cell surface and is designed to induce B cell tolerance.
Objective: This trial was designed to compare the ability of LJP
394 and placebo (PBO) to prevent renal flares (delay time to renal flare),
reduce aDNA, and decrease high-dose corticosteroid and cyclophosphamide
(CX) treatment.
Methods: Patients with aDNA and a history of SLE renal flare received
weekly infusions of PBO or 100mg of LJP 394 for 16 wks, followed by intermittent
dosing with PBO or 50mg of LJP 394 for 60 wks. A renal flare was recorded
if there was: a 1-2gm protein increase or a two-fold increase, depending
on the baseline (BL), in two 24hr collections of urine; a reproducible 20%
increase in serum creatinine (>0.3mg/dL); or a 2-grade increase in hematuria
with dysmorphic cells. Flares were recorded if physicians attributed the
abnormalities to SLE.
Results: The trial was stopped after an interim analysis showed
19 renal flares in the drug group and 23 in the PBO group. When patients'
pretreatment antibodies were analyzed for affinity to the drug, time to
renal flare was longer in drug-treated patients with high-affinity antibodies
(p=0.007).
Conclusion: LJP 394 appeared to provide clinical benefit to patients
with high-affinity antibodies to its oligonucleotide epitope. The drug was
well tolerated.
Outcomes |
Patients with high-affinity antibody |
All patients |
LJP 394 (n=91) |
PBO (n=95) |
LJP 394 (n=105) |
PBO (n=106) |
| Renal flares (over the first 16 wks) |
1 |
8 |
4 |
9 |
| Renal flares (over 18 mos) |
7 |
21 |
19 |
23 |
| Creatinine endpoint |
3 |
15 |
9 |
16 |
| Proteinuria endpoint |
6 |
11 |
14 |
13 |
| Hematuria endpoint |
0 |
3 |
2 |
3 |
| High-dose corticosteroid &/or CX (over 18 mos) |
13 |
34 |
23 |
38 |
| Anti-DNA: 30% decrease from BL @ 16wks |
40 |
13 |
43 |
16 |
Presented at The 64th Annual Scientific Meeting
of the American College of Rheumatology, Philadelphia, PA., Oct. 29
- Nov. 2, 2000.
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