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  • Review Article
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B-cell depletion in the treatment of lupus nephritis

Nature Reviews Nephrology volume 8, pages 505–514 (2012)Cite this article

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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.

Key Points

  • Over 20% of patients with lupus nephritis do not respond (or respond poorly) to standard induction therapy using cyclophosphamide or mycophenolate mofetil

  • Approximately two-thirds of patients with refractory or relapsing lupus nephritis respond to rituximab; complete B-cell depletion confers a favourable outcome, whereas relapse is related to B-cell reconstitution

  • Many adult patients (median 20%, range 5–73%) will relapse 1–4 years after B-cell depletion, but patients who relapse respond to further courses of rituximab

  • Rituximab therapy is safe and well tolerated in adult patients with lupus nephritis; the most common adverse events are mild to moderate infusion reactions and infections

  • 2–6% of adults with lupus nephritis have disease symptoms that are resistant to multiple therapies, including rituximab, which emphasizes the need for new therapeutic agents

  • Alternative B-cell-depleting monoclonal antibodies, such as anti-CD19 and anti-CD22 antibodies (epratuzumab), and anticytokine therapies (belimumab and atacicept), await evaluation in patients with lupus nephritis

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Figure 1: Potential B-cell-targeted therapies for lupus nephritis.
Figure 2: Rates of complete and partial responses to rituximab in patients with lupus nephritis.

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Authors and Affiliations

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

    Jon W. Gregersen

  2. The Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK

    David R. W. Jayne

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J. W. Gregersen researched the data for the article. D. R. W. Jayne contributed to discussions of the content, writing the article and to review and/or editing of the manuscript before submission.

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Correspondence to David R. W. Jayne.

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D. R. W. Jayne has received research grants and consultancy fees from Baxter, Biogen, GlaxoSmithKline, Genzyme, Merck Serono and Roche/Genentech, and research grants from Vifor Pharma. J. W. Gregersen declares no competing interests.

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Gregersen, J., Jayne, D. B-cell depletion in the treatment of lupus nephritis. Nat Rev Nephrol 8, 505–514 (2012). https://doi.org/10.1038/nrneph.2012.141

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