Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

B-cell-depletion therapy in SLE—what are the current prospects for its acceptance?

Abstract

Analogous to the successful introduction of biologic agents to treat rheumatoid arthritis, it was widely envisaged that similar successful studies would follow in systemic lupus erythematosus (SLE), as much was known about the etiopathogenesis of the disease and appropriate agents to block the key cells and molecules were available. The reality, however, has been different. The failure of rituximab, a monoclonal antibody that induces B-cell depletion, to meet its primary and secondary end points in trials of nonrenal SLE (EXPLORER) and renal (LUNAR) lupus nephritis has been disappointing given the success reported in many open-label studies. Concluding that B-cell-depletion therapy is not effective in SLE seems rather extreme. Further analysis of the as-yet unpublished results and their comparison with data from published studies might provide insight into whether B-cell depletion will eventually be accepted as a useful approach for the treatment of SLE.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Rahman, A. & Isenberg, D. A. Systemic lupus erythematosus. N. Engl. J. Med. 358, 929–939 (2008).

    Article  CAS  Google Scholar 

  2. Hostmann, A., Jacobi, A. M., Mei, H., Hiepe, F. & Dorner, T. Peripheral B cell abnormalities and disease activity in systemic lupus erythematosus. Lupus 17, 1064–1069 (2008).

    Article  CAS  Google Scholar 

  3. Reff, M. E. et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 83, 435–445 (1994).

    CAS  PubMed  Google Scholar 

  4. Merrill, J. T. et al. Efficacy and safety of rituximab in patients with moderately to severely active systemic lupus erythematosus (SLE): results from the randomized, double-blind phase II/III study EXPLORER (abstract 12). Presented at the American College of Rheumatology Annual Meeting, 2008 October, San Francisco, CA, USA.

  5. Li, E. K. et al. Is combination rituximab with cyclophosphamide better than rituximab alone in the treatment of lupus nephritis? Rheumatology (Oxford) 48, 892–898 (2009).

    Article  CAS  Google Scholar 

  6. Looney, R. J. et al. B cell depletion as a novel treatment for systemic lupus erythematosus: a phase I/II dose-escalation trial of rituximab. Arthritis Rheum. 50, 2580–2589 (2004).

    Article  CAS  Google Scholar 

  7. Vigna-Perez, M. et al. Clinical and immunological effects of rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study. Arthritis Res. Ther. 6, R83 (2006).

    Article  Google Scholar 

  8. Gottenberg J.-E. et al. Tolerance and short term efficacy of rituximab in 43 patients with systemic autoimmune diseases. Ann. Rheum. Dis. 64, 913–920 (2005).

    Article  CAS  Google Scholar 

  9. Smith, K. G., Jones, R. B., Burns, S. M. & Jayne, D. R. Long-term comparison of rituximab treatment for refractory systemic lupus erythematosus and vasculitis: remission, relapse and re-treatment. Arthritis Rheum. 54, 2970–2982 (2006).

    Article  CAS  Google Scholar 

  10. Gunnarson, I. et al. Histopathologic and clinical outcome of rituximab treatment in patients with cyclophosphamide-resistant proliferative lupus nephritis. Arthritis Rheum. 56, 1263–1272 (2007).

    Article  Google Scholar 

  11. Sutter, J. A. et al. A longitudinal analysis of SLE patients treated with rituximab (anti-CD20): factors associated with B lymphocyte recovery. Clin. Immunol. 126, 282–290 (2008).

    Article  CAS  Google Scholar 

  12. Albert, D. et al. Variability in the biological response to anti-CD20 B cell depletion in systemic lupus erythematosus. Ann. Rheum. Dis. 67, 1724–1731 (2008).

    Article  CAS  Google Scholar 

  13. Tokunaga, M. et al. Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system. Ann. Rheum. Dis. 66, 470–475 (2007).

    Article  CAS  Google Scholar 

  14. Sfikakis, P. P. et al. Remission of proliferative lupus nephritis following B cell depletion therapy is preceded by down-regulation of the T cell co-stimulatory molecule CD40 ligand: an open-label trial. Arthritis Rheum. 52, 501–513 (2005).

    Article  CAS  Google Scholar 

  15. Reynolds, J. A. et al. Effects of rituximab on resistant SLE disease including lung involvement. Lupus 18, 67–73 (2009).

    Article  CAS  Google Scholar 

  16. Leandro, M. J., Cambridge, G., Edwards, J. C., Ehrenstein, M. R. & Isenberg, D. A. B-cell depletion in the treatment of patients with systemic lupus erythematosus: a longitudinal analysis of 24 patients. Rheumatology (Oxford) 44, 1542–1545 (2005).

    Article  CAS  Google Scholar 

  17. Cambridge, G. et al. B-cell depletion therapy in systemic lupus erythematosus: effect on autoantibody and antimicrobial antibody profiles. Arthritis Rheum. 54, 3612–3622 (2006).

    Article  CAS  Google Scholar 

  18. Ng, K. P. et al. B cell depletion therapy in systemic lupus erythematosus: long-term follow-up and predictors of response. Ann. Rheum. Dis. 66, 1259–1262 (2007).

    Article  CAS  Google Scholar 

  19. Jónsdóttir, T. et al. Treatment of refractory SLE with rituximab plus cyclophosphamide: clinical effects, serological changes, and predictors of response. Ann. Rheum. Dis. 67, 330–334 (2008).

    Article  Google Scholar 

  20. Iannou, Y. et al. B cell depletion therapy for patients with systemic lupus erythematosus results in a significant drop in anticardiolipin antibody titers. Ann. Rheum. Dis. 67, 425–426 (2008).

    Article  Google Scholar 

  21. Leandro, M. J., Cambridge, G., Edwards, J. C., Ehrenstein, M. R. & Isenberg, D. A. An open study of B lymphocyte depletion in systemic lupus erythematosus. Arthritis Rheum. 46, 2673–2677 (2002).

    Article  Google Scholar 

  22. Tamimoto, Y. et al. A dose-escalation study of rituximab for treatment of systemic lupus erythematosus and Evans' syndrome: immunological analysis of B cells, T cells and cytokines. Rheumatology (Oxford) 47, 821–827 (2008).

    Article  CAS  Google Scholar 

  23. Ng, K. P. et al. Repeated B-cell depletion in treatment of refractory systemic lupus erythematosus. Ann. Rheum. Dis. 65, 942–945 (2006).

    Article  CAS  Google Scholar 

  24. Tanaka, Y. et al. A multicenter phase I/II trial of rituximab for refractory systemic lupus erythematosus. Mod. Rheumatol. 17, 191–197 (2007).

    Article  CAS  Google Scholar 

  25. Cambridge, G. et al. B cell depletion therapy in systemic lupus erythematosus: relationships among serum B lymphocyte stimulator levels, autoantibody profile and clinical response. Ann. Rheum. Dis. 67, 1011–1016 (2008).

    Article  CAS  Google Scholar 

  26. Lu, T. Y., Jónsdóttir, T., van Vollenhoven, R. F. & Isenberg, D. A. Prolonged B cell depletion following rituximab therapy in systemic lupus erythematosus. Ann. Rheum. Dis. 67, 1493–1494 (2008).

    Article  Google Scholar 

  27. Anolik, J. H. et al. The relationship of FcγRIIIa genotype to degree of B cell depletion by rituximab in the treatment of systemic lupus erythematosus. Arthritis Rheum. 48, 455–459 (2003).

    Article  CAS  Google Scholar 

  28. Sanz, I. The conundrum of B cell depletion in SLE. Nat. Rev. Rheumatol. 5, 304–305 (2009).

    Article  CAS  Google Scholar 

  29. Vallerskog, T. et al. Treatment with rituximab affects both the cellular and the humoral arm of the immune system in patients with SLE. Clin. Immunol. 122, 62–74 (2007).

    Article  CAS  Google Scholar 

  30. Calabrese, L. H., Molloy, E. S., Huang, D. & Ransohoff, R. M. Progressive multifocal leukencephalopathy in rheumatic diseases. Arthritis Rheum. 56, 2116–2128 (2007).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David A. Isenberg.

Ethics declarations

Competing interests

David A. Isenberg has acted as a consultant for Roche, but refused personal honoraria for this role, requesting instead that the support be given to local charity.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Favas, C., Isenberg, D. B-cell-depletion therapy in SLE—what are the current prospects for its acceptance?. Nat Rev Rheumatol 5, 711–716 (2009). https://doi.org/10.1038/nrrheum.2009.218

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrrheum.2009.218

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing