ARTHRITIS & RHEUMATISM Vol. 54, No. 2, February 2006, pp 421–432 DOI 10.1002/art.21625 © 2006, American College of Rheumatology SPECIAL ARTICLE The American College of Rheumatology Response Criteria for Proliferative and Membranous Renal Disease in Systemic Lupus Erythematosus Clinical Trials Renal Disease Subcommittee of the American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Response Criteria No new drugs have been approved for the treat- ment of systemic lupus erythematosus (SLE) in more than 30 years, and no drugs have been approved specif- ically for the treatment of lupus nephritis. The remark- able advances in our understanding of the pathogenetic mechanisms of SLE make it possible to target specific molecules, rather than treat the disease empirically with nonspecific antiinflammatory and immunosuppressive drugs. These developments and the discovery of other therapies, which may not be based on known mecha- nisms, make the rigorous evaluation of new therapies a priority in patient-oriented research. Controlled clinical trials are a challenge in SLE because of the difficulties in recruiting sufficient num- bers of patients, the varied phenotype of the disease, and the lack of valid biologic surrogates of lupus activity and damage for many organ systems, including the kidney. The lack of standard metrics has made it difficult to compare and pool the limited number of existing studies. The American College of Rheumatology (ACR) has organized several initiatives to facilitate the conduct of clinical trials that evaluate therapies for SLE. These include the development of a priori response criteria using measures of overall clinical disease activity (1), a proposal for criteria that define the efficacy of steroid- sparing agents (2), and recommendations for response criteria for major target organs. This article is the first in the series of response criteria for major target organs and describes the response criteria for lupus nephritis. We report herein the results of the work of the Renal Disease Subcommittee of the ACR Ad Hoc Committee on SLE Response Criteria from meetings held in May 2002 at the Heinrich-Heine-University in Du ¨sseldorf, Germany, and in February 2003 at the University of Toronto in Toronto, Ontario, Canada. We make recommendations for minimal essential end points, minimally significant clinical changes in these end points, and the covariates that should be reported in Supported by grants from the American College of Rheuma- tology, a Kirkland Scholar award, the SLE Foundation of New York, the Alliance for Lupus Research, the Lupus Erythematodes Selbsthil- fegemeinschaft e.V. Germany, the NIH (grants AR-47782 and R13- AR-47584-01), the Robert B. Brigham Arthritis and Musculoskeletal Diseases Clinical Research Center at Harvard University, the Swedish Medical Research Council (grant 13489), the Swedish Research Coun- cil (grant 12161), the Heinrich-Heine-University in Du ¨sseldorf, the Arthritis Research Centre of Canada at the University of British Columbia, the Arthritis Centre of Excellence and the Arthritis and Autoimmune Disease Centre at the University Health Network, University of Toronto, the Erik and Edith Fernstrom Foundation for Medical Research, the Office of the Clinical Director, Intramural Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Center for Advanced Methodological Support for Innovative SLE Clinical Trials (ASSIST). Members of the Renal Disease Subcommittee of the ACR Ad Hoc Committee on SLE Response Criteria are as follows: Matthew H. Liang, MD, MPH, Chair, Peter H. Schur, MD, Co-Chair, Paul Fortin, MD, MPH, Co-Chair, E. William St.Clair, MD, Co-Chair, James E. Balow, MD, Karen Costenbader, MD, MPH, Leslie Crofford, MD (American College of Rheumatology Committee on Research Liai- son), Paola de Pablo, MD, MPH, Mary Anne Dooley, MD, MPH, Axel Finckh, MD, MS, Caroline P. Gordon, MD, FRCP, Ingrid E. Lund- berg, MD, PhD, Alain Meyrier, MD, Ola Nived, MD, PhD, Claudio Ponticelli, MD, Matthias K. Schneider, MD, Ajay Singh, MD, and Daniel J. Wallace, MD. Dr. Schur is Editor of Up to Date in Rheumatology. Dr. Dooley has received consultancy fees (less than $10,000 each) from TEVA, ASPREVA, Genentech, GlaxoSmithKline, and Human Genomics Sciences. Dr. Lundberg owns stock in Pfizer. Dr. Ponticelli has received consultancy fees (more than $10,000 in 2004) from Novartis Italy. The American College of Rheumatology is an independent, professional, medical and scientific society which does not guarantee, warrant, or endorse any commercial product or service. Address correspondence to Matthew H. Liang, MD, MPH, Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, 75 Francis Street, PBB-3, Boston, MA 02115. Address reprint requests to the American College of Rheumatology, 1800 Century Place, Suite 250, Atlanta, GA 30345. Submitted for publication November 24, 2004; accepted in revised form November 7, 2005. 421