Spotlight on Research 2007

June 2007 (historical)

Biomarkers May Predict, and Corticosteroids Prevent, Severe Lupus Flares

Researchers supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) have demonstrated that two blood tests can predict severe flares in people with lupus who are clinically stable, and that moderate doses of corticosteroids can prevent flares in these individuals. The research, published in Arthritis and Rheumatism, suggests a possible preemptive strategy for managing lupus flares in some people with the disease.

Systemic lupus erythematosus, or lupus, is one of many immune system disorders known as autoimmune diseases. In autoimmune diseases, the immune system turns against parts of the body it is designed to protect by producing antibodies that react against a person's own tissue. These antibodies — as well as other substances called complement — serve as biomarkers for lupus and are indicators of many immune system problems that lead to clinical manifestations of the disease. Lupus is characterized by periods of illness, called flares, and periods of wellness, or remission.

"We focused on a limited but important population of patients who were clinically stable, but who had biomarkers that were suggestive of an impending flare," says author Chung-E Tseng, M.D. of New York University School of Medicine's Hospital for Joint Diseases. "We set out to tackle two concepts: one pertaining to the use of biomarkers to predict disease flares, and the other related to pre-emptive treatment with a moderate dose of prednisone, which is a common, inexpensive corticosteroid medication."

Tseng and her colleagues conducted a prospective, randomized, double-blind, placebo-controlled trial of 154 lupus patients who were evaluated for up to 18 months. Blood tests measuring lupus biomarkers — including anti-ds (double-stranded) DNA antibodies and complement C3a — were performed at monthly intervals. A subset of 41 patients who remained clinically stable but experienced increases in anti-dsDNA and C3a levels were then randomly assigned to receive prednisone or a placebo. Prednisone was given at a dosage of 30mg/day for 2 weeks, followed by 20mg/day for 1 week, and 10 mg/day for 1 week.

Within the next 90 days, six placebo-treated patients — but none of the prednisone-treated patients — experienced severe flares. In addition, those who received prednisone had improvement in overall disease activity. The authors concluded that short-term corticosteroid therapy may prevent flares in clinically stable lupus patients with elevated levels of C3a and anti-dsDNA. (In an editorial accompanying the article, Matthew Liang, M.D., M.P.H. of Brigham and Women's Hospital in Boston, estimates that C3a and anti-dsDNA were predictive of severe flares 40 percent of the time.)

Says Tseng, "For those of us who continue to have sleepless nights when our patients present with biomarkers suggestive of an impending flare but lack a clinical target to treat, the results of our study suggest that we may be on the right track in considering corticosteroids to prevent flares."

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov.

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Tseng CE, et al. 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. Arthritis Rheum 2006;54(11):3623-3632.