REVIEW www.nature.com/clinicalpractice/rheum Systemic lupus erythematosus—2005 annus mirabilis? David Isenberg* and Anisur Rahman INTRODUCTION A hundred years ago syphilis was regarded as ‘the great masquerader’—its modern equiva- lent is systemic lupus erythematosus (SLE). The clinical features and serological abnormalities that are present in patients with SLE are remark- ably diverse, and this is a formidable challenge for physicians both in terms of clinical assess- ment and treatment. A key therapeutic break- through in the late 1940s was the introduction of cortisone, initially for rheumatoid arthritis (RA), and soon afterwards for SLE. The notable anti-inflammatory properties of this drug were soon appreciated. Immunosuppressive drugs such as azathioprine, methotrexate and cyclo- phosphamide were introduced for the treat- ment of SLE in the 1960s and 1970s. These drugs helped to provide a major improvement in the outlook for patients with SLE; thus, where the 4-year survival was estimated to be just 50% in the 1950s, 1 the 15-year survival rate is now estimated to be around 80%. 2 Despite the improved prognosis of patients with SLE, clinical outcomes are far from ideal owing to the significant side effects of many of these now-conventional drugs, and the severity of the disease in a small, but significant number of the patients. For the 25 years from 1975 onwards, there was a worrying paucity of new therapeutic developments. By contrast, the last 5 years have seen a significant reversal of fortune, and 2005 saw the commencement of six or more large-scale, double-blind, random- ized, controlled trials in SLE (Table 1). What has brought about this notable transformation? The answer seems to lie in a ‘happy confluence’ of factors. First, several of the major pharma- ceutical companies have been persuaded that there are sufficient numbers of patients with SLE to make large-scale trials feasible. Although epidemiologic information relating to SLE is limited, extrapolation from data from the report by Johnson et al. 3 indicates that larger European countries, such as England, France and Germany, have several tens of thousands of patients with We are about to enter a new era in the treatment of patients with systemic lupus erythematosus (SLE). For the past 40 years hydroxychloroquine sulfate and corticosteroids, together with varying combinations of immunosuppressive drugs, have been the main treatments for SLE. Although effective for many patients, some patients fail to respond to these drugs and even more suffer from major side effects due to the generalized nature of the immunosuppression. In this article we review the remarkable confluence of new therapies ranging from newer immunosuppressive drugs with fewer side effects, such as mycophenolate mofetil, to the more targeted approaches offered by biological agents. These agents have been designed to block molecules such as CD20, CD22 and interleukin-10 that are thought to have an integral part in the development of SLE. This wolf might not yet be about to become extinct but its survival is increasingly under threat! KEYWORDS anticytokine therapy, clinical trials, immunosuppression, systemic lupus erythematosus D Isenberg is the Academic Director of the Center for Rheumatology and a Professor of Rheumatology, and A Rahman is a Senior Lecturer and Honorary Consultant in Rheumatology at University College London Hospitals, London, UK. Correspondence *Centre for Rheumatology, University College London, Room 331, Windeyer Building, 46 Cleveland Street, London W1T 4JF, UK d.isenberg@ucl.ac.uk Received 20 June 2005 Accepted 17 October 2005 www.nature.com/clinicalpractice doi:10.1038/ncprheum0116 REVIEW CRITERIA Published articles for inclusion in this Review were identified from the authors’ extensive records of papers on systemic lupus erythematosus dating from 1955 to date. All papers identified were English-language full-text papers. SUMMARY MARCH 2006 VOL 2 NO 3 NATURE CLINICAL PRACTICE RHEUMATOLOGY 145 Nature Publishing Group ©2006