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B-cell depletion in the treatment of lupus nephritis.

Abstract

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is clinically heterogeneous and affects multiple organs. Lupus nephritis is the most frequent severe manifestation of SLE. Conventional immunosuppressive therapy has increased the life expectancy of patients diagnosed with lupus nephritis, but only 70-80% of patients respond to this treatment and its adverse effects are considerable. B cells are central to the pathogenesis of SLE and are, therefore, an attractive therapeutic target. B-cell depletion has been used successfully to treat other autoimmune diseases, such as rheumatoid arthritis and antineutrophil cytoplasmic antibody-associated vasculitis, and many case reports and small nonrandomized trials of B-cell-depleting agents in patients with lupus nephritis have reported positive results. By contrast, two large placebo-controlled trials designed to investigate the efficacy of the B-cell-depleting agents rituximab and ocrelizumab as a treatment for lupus nephritis, failed to meet their primary efficacy end points (LUNAR and BELONG, respectively). This Review discusses the current evidence on the use of B-cell depletion in the treatment of lupus nephritis, which is derived from case studies and clinical trials including a total of over 800 patients.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Nephrology, Aarhus University Hospital, Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark.

    Source

    Nature reviews. Nephrology 8:9 2012 Sep pg 505-14

    MeSH

    Antibodies, Monoclonal, Humanized
    Antibodies, Monoclonal, Murine-Derived
    B-Lymphocytes
    Female
    Follow-Up Studies
    Humans
    Immunosuppression
    Lupus Nephritis
    Lymphocyte Depletion
    Male
    Randomized Controlled Trials as Topic
    Risk Assessment
    Rituximab
    Severity of Illness Index
    Treatment Outcome

    Pub Type(s)

    Journal Article
    Review

    Language

    eng

    PubMed ID

    22801948

    Citation

    Gregersen, Jon W., and David R W. Jayne. "B-cell Depletion in the Treatment of Lupus Nephritis." Nature Reviews. Nephrology, vol. 8, no. 9, 2012, pp. 505-14.
    Gregersen JW, Jayne DR. B-cell depletion in the treatment of lupus nephritis. Nat Rev Nephrol. 2012;8(9):505-14.
    Gregersen, J. W., & Jayne, D. R. (2012). B-cell depletion in the treatment of lupus nephritis. Nature Reviews. Nephrology, 8(9), pp. 505-14. doi:10.1038/nrneph.2012.141.
    Gregersen JW, Jayne DR. B-cell Depletion in the Treatment of Lupus Nephritis. Nat Rev Nephrol. 2012;8(9):505-14. PubMed PMID: 22801948.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - B-cell depletion in the treatment of lupus nephritis. AU - Gregersen,Jon W, AU - Jayne,David R W, Y1 - 2012/07/17/ PY - 2012/7/18/entrez PY - 2012/7/18/pubmed PY - 2013/1/17/medline SP - 505 EP - 14 JF - Nature reviews. Nephrology JO - Nat Rev Nephrol VL - 8 IS - 9 N2 - Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is clinically heterogeneous and affects multiple organs. Lupus nephritis is the most frequent severe manifestation of SLE. Conventional immunosuppressive therapy has increased the life expectancy of patients diagnosed with lupus nephritis, but only 70-80% of patients respond to this treatment and its adverse effects are considerable. B cells are central to the pathogenesis of SLE and are, therefore, an attractive therapeutic target. B-cell depletion has been used successfully to treat other autoimmune diseases, such as rheumatoid arthritis and antineutrophil cytoplasmic antibody-associated vasculitis, and many case reports and small nonrandomized trials of B-cell-depleting agents in patients with lupus nephritis have reported positive results. By contrast, two large placebo-controlled trials designed to investigate the efficacy of the B-cell-depleting agents rituximab and ocrelizumab as a treatment for lupus nephritis, failed to meet their primary efficacy end points (LUNAR and BELONG, respectively). This Review discusses the current evidence on the use of B-cell depletion in the treatment of lupus nephritis, which is derived from case studies and clinical trials including a total of over 800 patients. SN - 1759-507X UR - https://www.unboundmedicine.com/medline/citation/22801948/B_cell_depletion_in_the_treatment_of_lupus_nephritis_ L2 - http://dx.doi.org/10.1038/nrneph.2012.141 DB - PRIME DP - Unbound Medicine ER -