The effect of moderate-dose corticosteroids in preventing severe flares in patients with serologically active, but clinically stable, systemic lupus erythematosus: findings of a prospective, randomized, double-blind, placebo-controlled trial.
OBJECTIVE
Serial measurements of anti-double-stranded DNA (anti-dsDNA) and complement are routine in the management of systemic lupus erythematosus (SLE), but their utility as biomarkers in preemptive treatment to prevent flares remains a subject of controversy. We hypothesized that concomitant elevation of anti-dsDNA and C3a can predict SLE activity in patients with stable or inactive disease and that short-term treatment with corticosteroids can avert flares.


METHODS
In this prospective, randomized, double-blind, placebo-controlled trial, 154 patients were evaluated monthly for up to 18 months, with measurements of C3a, C3, C4, CH50, and anti-dsDNA levels. Patients who remained clinically stable but showed serologic evidence of an SLE flare (elevation of both the anti-dsDNA level by 25% and the C3a level by 50% over the previous 1-2 monthly visits) were randomized to receive either prednisone or placebo therapy at a dosage of 30 mg/day for 2 weeks, 20 mg/day for 1 week, and 10 mg/day for 1 week.


RESULTS
Forty-one patients (21 randomized to prednisone and 20 randomized to placebo) experienced a serologic flare. Analysis of severe flares occurring <or=90 days from randomization revealed that 6 occurred in patients taking placebo and none occurred in patients taking prednisone (P = 0.007). Severe flares resulted in an increase in the prednisone dosage to >40 mg/day and/or the addition of an immunosuppressive agent. Furthermore, improvement in scores on the Systemic Lupus Erythematosus Disease Activity Index, decreased levels of anti-dsDNA antibodies, and increased levels of C4 occurred 1 month after initiation of prednisone treatment.


CONCLUSIONS
These preliminary data support our hypothesis that in a subset of clinically stable SLE patients with a combination of elevated C3a and anti-dsDNA levels, short-term corticosteroid therapy may avert a severe flare.
Tseng
Chung-E
CE
New York University School of Medicine, Hospital for Joint Diseases, New York, New York 10003, USA. chung_e_tseng@hotmail.com
Buyon
Jill P
JP
Kim
Mimi
M
Belmont
H Michael
HM
Mackay
Meggan
M
Diamond
Betty
B
Marder
Galina
G
Rosenthal
Pamela
P
Haines
Kathleen
K
Ilie
Virginia
V
Abramson
Steven B
SB
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D002648:Child; D015926:Complement C3a / Q000378:metabolism; D004247:DNA / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D010919:Placebos; D011241:Prednisone / Q000008:administration & dosage*; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
D001323:Autoantibodies; D005938:Glucocorticoids; D010919:Placebos; D015926:Complement C3a; D004247:DNA; D011241:Prednisone