title: Challenges and opportunities in SLE clinical trials.
abstract: OBJECTIVE
  To provide an update on the field of clinical trials in systemic lupus erythematosus (SLE). This review will examine failed and successful clinical trials in SLE in order to draw lessons and determine the optimal ways forward.
  
  
  RESULTS
  Over the past decade, many clinical trials in SLE met with limited success, but in the past 2 years several SLE clinical trials have been successful. The two large phase III randomized controlled trials (RCTs) of belimumab achieved their primary endpoints and resulted in food and drug administration and European medicines agency approval of the drug. Characteristics of these trials were, among other things, a very large number of patients (>800 each), compound clinical endpoints, and a flexible design with regards to concomitant medication use. Likewise, large randomized controlled trials with mycophenolate mofetil, although nominally unsuccessful, clearly demonstrated the clinical benefit of this drug in lupus nephritis. Posthoc analyses of several failed trials involving abatacept and rituximab revealed design elements and/or outcomes that might have changed the outcomes of these studies. Many smaller trials have also been reported, in some instances with surprisingly positive results.
  
  
  CONCLUSIONS
  An improved understanding of specific design features in SLE clinical trials combined with robust outcomes will make it possible more effectively to design and conduct clinical trials in SLE.
authors.affiliation: Unit for Clinical Therapy Research, Inflammatory Diseases, The Karolinska Institute, Stockholm, Sweden. ronald.van.vollenhoven@ki.se
authors.forename: Ronald F
authors.initials: RF
authors.lastname: van Vollenhoven
mesh_terms: D000069594:Abatacept; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D000069283:Rituximab; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab; C511911:belimumab; D000069594:Abatacept