Pragmatic approaches to therapy for systemic lupus erythematosus

Journal name:
Nature Reviews Rheumatology
Volume:
10,
Pages:
97–107
Year published:
DOI:
doi:10.1038/nrrheum.2013.157
Published online

Abstract

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with substantial clinical heterogeneity. Current treatments for SLE are effective at reducing morbidity and mortality but fail to provide a cure, and they frequently have adverse effects. Traditional treatments include NSAIDs and antimalarial agents, which are the first-line therapies for mild SLE. In addition, glucocorticoids and cytotoxic or immunosuppressive agents—such as azathioprine, mycophenolate mofetil, cyclophosphamide, cyclosporine and methotrexate —are used for SLE with organ involvement. Advances in understanding the immunopathogenesis of SLE have led to the development of targeted immunotherapies, such as the anti-BAFF antibody belimumab, which has been approved as an add-on therapy for patients who have active disease despite receiving standard therapy. This Review presents an overview of the current therapies and nonpharmacological management approaches for SLE, and discusses the best approaches for treating specific disease manifestations such as lupus nephritis, neuropsychiatric lupus and cutaneous lupus erythematosus.

At a glance

Figures

  1. Algorithm for the treatment of SLE.
    Figure 1: Algorithm for the treatment of SLE.

    Abbreviations: CLE, cutaneous lupus erythematosus; CVD, cardiovascular disease; IVIG, intravenous immunoglobulin; MMF, mycophenolate mofetil; SLE, systemic lupus erythematosus.

  2. Mechanisms of action of targeted therapies in SLE.
    Figure 2: Mechanisms of action of targeted therapies in SLE.

    B cells have a central role in the pathogenesis of SLE at multiple levels, through both antibody-dependent and antibody-independent mechanisms. B cells are the precursors of antibody-secreting plasma cells, and autoantibodies contribute to autoimmunity by immune-complex-mediated, type III hypersensitivity reactions involving TLR co-stimulation and type II antibody-dependent cytotoxicity; they also promote the production of pathogenic cytokines such as IFN-α and TNF by innate immune cells. Autoantibody-independent B-cell functions include antigen presentation, T-cell activation and polarization, and dendritic cell modulation. Those functions require the ability of B cells to produce regulatory cytokines, chemokines and lymphangiogenic growth factors (such as IL-10, IL-6, IFN-γ and lymphotoxin-α).154, 155, 156 Numerous molecules in these pathways might provide suitable targets for SLE therapy. Abbreviations: BAFF, B-cell activating factor; BAFFR, BAFF receptor; BCMA, B-cell maturation antigen; CTLA4-Ig, cytotoxic T-lymphocyte antigen 4–immunoglobulin; DC, dendritic cell; ICOS, inducible T-cell co-stimulator; ICOSL, ICOS ligand; IFN, interferon; JAK3, Janus kinase 3; SLE, systemic lupus erythematosus; SYK, spleen tyrosine kinase; TACI, transmembrane activator and CAML interactor; TLR, Toll-like receptor. Permission obtained from SAGE © Xiong, W. & Lahita, R. Ther. Adv. Musculoskelet. Dis. 3, 255266 (2011).88

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Affiliations

  1. Newark Beth Israel Medical Centre, 201 Lyons Avenue, Newark, NJ 07112, USA

    • Wen Xiong &
    • Robert G. Lahita

Contributions

Both authors contributed to discussing the content of the article, researching data and writing the manuscript. In addition, R. G. Lahita reviewed/edited the manuscript before submission.

Competing interests statement

R. G. Lahita declares that he has received consultancy fees and honoraria for speaking from GlaxoSmithKline. W. Xiong declares no competing interests.

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  • Wen Xiong

    Wen Xiong is an attending rheumatologist at Newark Beth Israel Medical Centre, NJ, USA. She is board-certified in internal medicine and rheumatology and is a fellow of the American College of Rheumatology. Her research interests focus on systemic lupus erythematosus, systemic sclerosis and vasculitis. She completed rheumatology fellowship at Thomas Jefferson University Hospitals, Philadelphia, PA, USA, in 2010, and medical residency at Sound Shore Medical Centre of Westchester, NY, USA, in 2008. Previously, Wen Xiong was a physical therapist and received a Master of Science in physical therapy at New York Medical College, NY. She also worked as a postdoctoral research scientist at Columbia-Presbyterian Medical Centre, NY. A first-generation Chinese-American, Wen Xiong earned her medical degree at West China University of Medical Sciences in China.

  • Robert G. Lahita

    Robert G. Lahita is the Chairman of Medicine at Newark Beth Israel Medical Centre and a senior attending rheumatologist. He is also Professor of Medicine and Adjunct Professor of Molecular Biology and Biochemistry at Rutgers, the New Jersey Medical School, USA. Robert Lahita conducts both clinical and basic research in the area of systemic lupus erythematosus and other autoimmune diseases. He graduated from the Jefferson Medical College, Philadelphia, PA, in 1972 and trained in rheumatology at Rockefeller University, New York, in the laboratory of Henry G. Kunkel. He completed his internal medicine training at Cornell-Weill Medical College, New York Presbyterian Hospital.

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    Summary of Targeted Immunotherapies for SLE

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