Human Clinical Trials in Lupus Nephritis

Improved patient survival after treatment of lupus nephritis with corticosteroids, immunosuppressants, and renal replacement therapy allows greater emphasis on long-term management issues. In particular, the recent focus has been on therapies to treat nephritis with fewer adverse effects compared with cyclophosphamide and immunosuppressive regimens. Issues complicating clinical trial design in lupus nephritis have severely limited comparisons across trials. These issues, including recognition and stratification of high-risk populations, comparable remission and response criteria, and appropriate use and interpretation of activity and damage indices have been the subject of much discussion and emerging consensus. Mycophenolate mofetil (MMF) has been used in the field of transplantation for more than 10 years. After initial anecdotal reports describing the benefits of MMF in the treatment of lupus nephritis, randomized controlled trials have established a role for MMF in the treatment of lupus nephritis. A host of newer agents including rituximab, abatacept, and monoclonal antibodies blocking costimulatory targets are in current clinical trials for lupus nephritis. As long-term outcomes in lupus nephritis improve, the toxicity of therapy and risk of relapse become increasingly important determinants of the choice of therapeutic agents.