Rituximab for Rheumatoid Arthritis

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     To the Editor: Edwards et al. (June 17 issue)1 show that the anti-CD20 monoclonal antibody rituximab provides effective therapy for rheumatoid arthritis. They report that the effects of rituximab are not associated with changes in serum immunoglobulin levels, suggesting that this anti-CD20 antibody alleviates symptoms associated with rheumatoid arthritis through an antibody-independent mechanism. In their study, serious bacterial infections occurred in only four patients (3.3 percent) in the rituximab groups. Nevertheless, we suspect that the use of this therapeutic protein may lead to severe infectious diseases such as tuberculosis, sepsis, and viremia.

    The target of rituximab, CD20, has been reported to associate with major-histocompatibility-complex (MHC) class II molecules and to have an important role in the activation of B cells.2 Consequently, anti-antigen presentation may be one of the antibody-independent mechanisms by which rituximab functions. If this is the case, clinicians should be aware that the use of rituximab could allow for the development of severe infections, especially in cases in which functions of antigen presentation play an important role in disease protection.

    Hiroshi Okamoto, M.D., Ph.D.

    Naoyuki Kamatani, M.D., Ph.D.

    Tokyo Women's Medical University

    Tokyo 162-0054, Japan

    hokamoto@parkcity.ne.jp

    References

    Edwards JC, Szczepanski L, Szechinski J, et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 2004;350:2572-2581.

    Leveille C, Castaigne JG, Charron D, Al-Daccak R. MHC class II isotype-specific signaling complex on human B cells. Eur J Immunol 2002;32:2282-2291.

    Dr. Edwards replies: Okamoto and Kamatani seem to have failed to notice that autoantibody levels — rheumatoid factor in our study, and anti-citrullinated peptide antibodies in more detailed studies1 — fall substantially after rituximab therapy. The time course of remission and subsequent relapse correlates with the level of the autoantibody rather than with that of the B cells.1 There is no reason at present to think that anti-CD20 acts through an antibody-independent mechanism. Removal of B cells will remove B-cell–based antigen presentation (whatever the function of CD20 or its relation to MHC class II). However, there is no evidence of, or reason to expect, an effect on antigen presentation by macrophages or dendritic cells. The suggestion that the removal of B cells may increase the risk of tuberculosis or viral infection seems illogical and speculative. A large body of evidence on the risk of infection after rituximab therapy in patients with lymphoma and a growing database on rheumatic disease do not support the suggestion.2 The possible small increase in the risk of lower respiratory infection2 seems commensurate with the inability to make new antibody.

    Jonathan C.W. Edwards, M.D.

    University College London

    London W1P 9PG, United Kingdom

    jo.edwards@ucl.ac.uk

    References

    Cambridge G, Leandro MJ, Edwards JCW, et al. Serological changes following B lymphocyte depletion therapy for rheumatoid arthritis. Arthritis Rheum 2003;48:2146-2154.

    Edwards JCW, Leandro MJ, Cambridge G. B lymphocyte depletion therapy with rituximab in rheumatoid arthritis. Rheum Dis Clin North Am 2004;30:393-403.

    http://www.100md.com/html/DirDu/2006/11/29/30/66/60.htm