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B-cell targeted therapies in rheumatoid arthritis and systemic lupus erythematosus

Nature Clinical Practice Rheumatology volume 2, pages 20–27 (2006)Cite this article

Abstract

B cells appear to have a central role in the immunopathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE); both autoantibody production and B-cell anomalies are characteristic of these diseases. With the recent availability of biologic agents that can deplete B cells or block their function in vivo, it has become possible to target B cells therapeutically. Evidence strongly suggests that novel B-cell targeting agents are effective. In addition, the mechanistic specificity of B-cell targeted approaches, combined with the ability to test them in large randomized controlled trials, will provide an unprecedented opportunity to study the precise roles of B cells in the immunopathogenesis of RA and SLE. The largest volume of information is available for rituximab, a chimeric monoclonal antibody that depletes B cells by binding to the CD20 cell-surface antigen. Information from multiple investigator-sponsored trials and from off-label use suggests efficacy of this antibody in RA, SLE, and other autoimmune syndromes. Randomized controlled trials have also provided solid evidence for the efficacy of rituximab in RA and are ongoing in SLE. Other therapeutic agents supported by controlled data include cytotoxic T-lymphocyte-associated protein 4 immunoglobulin and antibodies against the interleukin-6 receptor and the B-cell survival molecule BLyS. Additional agents and targets are in earlier stages of development. The concerns about infectious complications have so far not proven to be justified. We can reasonably expect important advances in the understanding and treatment of RA and SLE in the next 5–10 years, as B-cell targeting methods become more widespread and sophisticated.

Key Points

  • B cells are important in the pathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), not only because they produce autoantibodies, but also because of their role in anomalous immunoregulation

  • The availability of a B-cell-depleting therapy (rituximab) has greatly facilitated B-cell targeted trials in SLE and RA; efficacy has been demonstrated in randomized controlled trials in RA, but evidence of rituximab's efficacy in SLE is, so far, anecdotal

  • Other approaches to B-cell targeting include anticytokine and anti-B cell-surface molecule techniques, as well as blockade of costimulatory signals

  • Perhaps surprisingly, recurrent infections have not been a safety issue; given the biologic effectiveness of these B-cell targeting agents, however, ongoing vigilance will be essential

  • We hope to learn more about the roles of B cells in RA and SLE by the use of these agents; it will be particularly important that mechanistic studies accompany randomized controlled trials in this area

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Figure 1: B-cell development.

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Authors and Affiliations

  1. Professor of Medicine and Pathology, University of Pennsylvania, School of Medicine, Philadelphia, USA

    Robert Eisenberg

  2. Professor of Medicine and Pediatrics, University of Pennsylvania, School of Medicine, Philadelphia, USA

    Daniel Albert

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  1. Robert Eisenberg
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  2. Daniel Albert
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Correspondence to Robert Eisenberg.

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Competing interests

R Eisenberg and D Albert are participating in trials with rituximab and epratuzumab, for which they receive monetary support.

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Eisenberg, R., Albert, D. B-cell targeted therapies in rheumatoid arthritis and systemic lupus erythematosus. Nat Rev Rheumatol 2, 20–27 (2006). https://doi.org/10.1038/ncprheum0042

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