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

Abstract

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 ≤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. Conclusion 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.