State of the Art REVIEW
Advances in the management of systemic lupus erythematosus Eric F Morand, 1,2 Ruth Fernandez-Ruiz, 3 Ashira Blazer, 3 Timothy B Niewold 3
Abstract Systemic lupus erythematosus (SLE) is a severe multisystem autoimmune disease that can cause injury in almost every body system. While considered a classic example of autoimmunity, it is still relatively poorly understood. Treatment with immunosuppressive agents is challenging, as many agents are relatively non- specific, and the underlying disease is characterized by unpredictable flares and remissions. This State of The Art Review provides a comprehensive current summary of systemic lupus erythematosus based on recent literature. In basic and translational science, this summary includes the current state of genetics, epigenetics, differences by ancestry, and updates about the molecular and immunological pathogenesis of systemic lupus erythematosus. In clinical science, the summary includes updates in diagnosis and classification, clinical features and subphenotypes, and current guidelines and strategies for treatment. The paper also provides a comprehensive review of the large number of recent clinical trials in systemic lupus erythematosus. Current knowns and unknowns are presented, and potential directions for the future are suggested. Improved knowledge of immunological pathogenesis and the molecular differences that exist between patients should help to personalize treatment, minimize side effects, and achieve better outcomes in this difficult disease.
1 School of Clinical Sciences, Monash University, Melbourne, VIC, Australia 2 Department of Rheumatology, Monash Health, Melbourne, VIC, Australia 3 Hospital for Special Surgery, New York, NY, USA Correspondence to: Eric F Morand eric.morand@monash.edu Cite this as: BMJ 2023;383:073980 http://dx.doi.org/10.1136/bmj- 2022-073980 Series explanation: State of the Art Reviews are commissioned on the basis of their relevance to academics and specialists in the US and internationally. For this reason they are written predominantly by US authors.
of targeted treatments have resulted in paradigm changes in patient outcomes. Moreover, challenges in the measurement of treatment response continue to contribute to trial failures, and the endpoints used in trials are neither used routinely in clinical practice nor reflected in management guidelines. Clearly, much remains to be done to improve the lives of patients with systemic lupus erythematosus. This review summarizes the latest approaches in the management of systemic lupus erythematosus, focusing on independently confirmed evidence, for example, in independent clinical or laboratory studies. Despite some areas being underpinned by robust evidence, major gaps in knowledge remain. We suggest objectives for future research to bridge these gaps and improve the lives and life expectancy of patients with systemic lupus erythematosus. Epidemiology of systemic lupus erythematosus The incidence and prevalence of systemic lupus erythematosus vary widely between global regions. The differences in epidemiological estimates in world populations are likely due to differences in access to care in different regions, environmental exposures and socioeconomic status, genetic risk factors, and heterogeneity in features of systemic
Introduction Most clinicians learnt at medical school that systemic lupus erythematosus (SLE, or lupus) is the archetypal multisystem autoimmune disease. Patients classified as having systemic lupus erythematosus manifest immune mediated inflammatory injury in virtually every organ system, and therefore, lupus can present across all fields of medicine. This well known clinical heterogeneity results in many difficulties, including how to make the diagnosis or standardize treatment approaches. We now also know that patients clinically classified as having systemic lupus erythematosus represent a cluster of differing molecular pathologies that could explain these diverse phenotypes. The challenges posed by the combination of clinical and biological heterogeneity have contributed to a paucity of major breakthroughs in the treatment of systemic lupus erythematosus. Even though recent years have seen the approval of three new treatments for systemic lupus erythematosus and lupus nephritis, the management of most patients has changed little since the last century, with long term outcomes characterized by high morbidity and mortality. This stagnation is in stark contrast to other autoimmune diseases such as rheumatoid arthritis, where the adoption of treat-to-target strategies and the use
the bmj | BMJ 2023;383:073980 | doi: 10.1136/bmj-2022-073980
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