Thrombosis and Systemic Lupus Erythematosus: The Hopkins Lupus Cohort Perspective

The antimalarial drug hydroxychloroquine is thought to be effective in controlling some of the manifestations of systemic lupus erythematosus, but its effectiveness has not been demonstrated conclusively. We conducted a six-month, randomized, double-blind, placebo-controlled study of the effect of discontinuing hydroxychloroquine sulfate treatment in 47 patients with clinically stable systemic lupus erythematosus. The patients were randomly assigned to continue their same dose of hydroxychloroquine (n = 25) or to receive placebo (n = 22) for 24 weeks. Ten patients in each group were also taking prednisone. The relative risk of a clinical flare-up, defined as the development of specific clinical manifestations of systemic lupus erythematosus or an increase in their severity, was 2.5 times higher (95 percent confidence interval, 1.08 to 5.58) in the patients taking placebo than in those continuing to take hydroxychloroquine (16 of 22 patients vs. 9 of 25 had flare-ups), and the time to a flare-up was shorter (P = 0.02). The relative risk of a severe exacerbation of disease that required withdrawal from the study was 6.1 times higher (95 percent confidence interval, 0.72 to 52.44) for the patients taking placebo (5 of 22 patients vs. 1 of 25 had severe exacerbations of disease). Changes in the dose of prednisone were not different in the two groups. Patients with quiescent systemic lupus erythematosus who are taking hydroxychloroquine are less likely to have a clinical flare-up if they are maintained on the drug.

To determine the effect of prednisone dose and hydroxychloroquine dose on the coronary artery disease risk factors serum cholesterol level, mean arterial blood pressure, and weight in patients with systemic lupus erythematosus. A longitudinal cohort study of 264 patients with systemic lupus erythematosus was conducted. For all patients in the cohort, serum cholesterol, mean arterial pressure, weight, prednisone dose, hydroxychloroquine dose, and other potential confounding variables were recorded at each visit. Regression analysis appropriate for longitudinal data was used to assess the effect of prednisone on serum cholesterol and mean arterial pressure. To assess the effect of prednisone on weight, patients' weights were compared 90 days before and after a 10-mg or 20-mg increase in prednisone. A total of 3,027 patient visits were analyzed. In the regression model for serum cholesterol, a change in prednisone dose of 10 mg was associated with a change in cholesterol of 7.5 +/- 1.46 (SE) mg% after adjustment for the other significant variables in the model, including sex, race, hydroxychloroquine dose, and proteinuria. In the regression model for hydroxychloroquine, the 200-mg and the 400-mg dose were both associated with lower serum cholesterol (8.9 +/- 3.44 SE mg%). In the regression model for mean arterial blood pressure, a 10-mg change in prednisone dose led to a change in mean arterial blood pressure of 1.1 mm Hg after adjustment for age, weight, and antihypertensive drug use. A 10-mg increase in prednisone dose was associated with a mean weight change of 5.50 +/- 1.23 (SE) lb. Changes in prednisone dose led to definable changes in risk factors for coronary artery disease, even after adjustment for other variables known to affect these risk factors. According to longitudinal regression analysis, hydroxychloroquine therapy was associated with lower serum cholesterol.