A double-blind, placebo-controlled, clinical trial of dehydroepiandrosterone in severe systemic lupus erythematosus

Objective: To determine if dehydroepiandrosterone (DHEA) is beneficial in s evere systemic lupus erythematosus (SLE). Methods: A double-blinded, placebo-controlled, randomized clinical trial in 21 patients with severe and active SLE, manifestated primarily by nephriti s, serositis or hematological abnormalities. In addition to conventional tr eatment with corticosteroids +/- immunosuppressives, patients received DHEA 200 mg/d vs placebo for 6 months, followed by a 6-month open label period. The primary outcome was a prospectively defined responder analysis, based on a quantitatively specified improvement of the principal severe lupus man ifestation at 6 months. Results: Nineteen patients were available for evaluation at 6 months. Basel ine imbalance between the groups was noted, with the DHEA group having grea ter disease activity at baseline (P < 0.05 by physician's global assessment ). Eleven patients were responders: 7/9 patients on DHEA vs 4/10 patients o n placebo (P < 0.10). Of the secondary outcomes, mean improvement in SLE di sease activity index (SLE-DAI) score was greater in the DHEA group (-10.3+/ -3.1 vs -3.9 +/- 1.4, P < 0.07). Bone mineral density at the lumbo-sacral s pine showed significant reduction in the placebo group, but was maintained in the DHEA group. Conclusion: DHEA therapy, when added to conventional treatment for severe S LE, may at most have a small added benefit with respect to lupus outcomes, but baseline imbalances in the study population limit the generalizability of the results. DHEA appears to have a protective effect with respect to co rticosteroid-induced osteopenia in such patients.