Systemic lupus erythematosus trials: successes and issues

The purpose of this review is to discuss the most recent published clinical trials for systemic lupus erythematosus and to identify important issues that have arisen in association with the search for new therapies for systemic lupus erythematosus, as well as new regimens or indications for the use of "standard-of-care" agents such as corticosteroids and cyclophosphamide.

Important developments have occurred during the past 2 years as interest in this area has increased, largely because of the participation of pharmaceutical and biotechnical companies in the development and testing of novel agents for systemic lupus erythematosus. Several important large-scale, multicenter, randomized controlled trials have been completed, but none has yet resulted in a new, approved indication for systemic lupus erythematosus. Many issues in the identification of new therapeutic modalities remain. These include the fact that a majority of published reports include either small numbers of patients in controlled trials that lack statistical power to draw conclusions, or are uncontrolled anecdotal series or individual case reports. Among the larger controlled trials, a pervasive issue in the failure to reach statistical significance may be the initial study design. Inclusion of patients with mild and/or stable disease activity does not allow for an effect size sufficient to show differences in treatment arms without recruitment of very large numbers of subjects. Finally, several potentially important trials have been reported only in abstract form to date. Further assessment of the results must await formal publication of these studies.