Abetimus sodium for renal flare in systemic lupus erythematosus: results of a randomized, controlled phase III trial.
OBJECTIVE
To investigate whether treatment with abetimus delays renal flare in patients with lupus nephritis. Secondary objectives included evaluation of the effect of abetimus on C3 levels, anti-double-stranded DNA (anti-dsDNA) antibody levels, use of high-dose corticosteroids and/or cyclophosphamide, and major systemic lupus erythematosus (SLE) flare.


METHODS
We conducted a randomized, placebo-controlled study of treatment with abetimus at 100 mg/week for up to 22 months in SLE patients. Three hundred seventeen patients with a history of renal flare and anti-dsDNA levels >15 IU/ml were randomized to a treatment group (158 abetimus, 159 placebo); 298 (94%) were enrolled in the intent-to-treat (ITT) population (145 abetimus, 153 placebo), based on the presence of high-affinity antibodies for the oligonucleotide epitope of abetimus at baseline screening.


RESULTS
Abetimus did not significantly prolong time to renal flare, time to initiation of high-dose corticosteroid and/or cyclophosphamide treatment, or time to major SLE flare. However, there were 25% fewer renal flares in the abetimus group compared with the placebo group (17 of 145 abetimus-treated patients [12%] versus 24 of 153 placebo-treated patients [16%]). Abetimus treatment decreased anti-dsDNA antibody levels (P < 0.0001), and reductions in anti-dsDNA levels were associated with increases in C3 levels (P < 0.0001). More patients in the abetimus group experienced > or =50% reductions in proteinuria at 1 year, compared with the placebo group (nominal P = 0.047). Trends toward reduced rates of renal flare and major SLE flare were noted in patients treated with abetimus who had impaired renal function at baseline. Treatment with abetimus for up to 22 months was well tolerated.


CONCLUSIONS
Abetimus at 100 mg/week significantly reduced anti-dsDNA antibody levels but did not significantly prolong time to renal flare when compared with placebo. Multiple positive trends in renal end points were observed in the abetimus treatment group.
Cardiel
Mario H
MH
Hospital General Dr Miguel Silva, Morelia, Michoacán, Mexico.
Tumlin
James A
JA
Furie
Richard A
RA
Wallace
Daniel J
DJ
Joh
Tenshang
T
Linnik
Matthew D
MD
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D003176:Complement C3 / Q000378:metabolism; D003520:Cyclophosphamide / Q000627:therapeutic use; D004247:DNA / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000188:drug therapy; D008181:Lupus Nephritis / Q000188:drug therapy / Q000209:etiology* / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000888:Antibodies, Anti-Idiotypic; D003176:Complement C3; D009841:Oligonucleotides; D003520:Cyclophosphamide; D004247:DNA; C094104:abetimus