Long-term comparison of rituximab treatment for refractory systemic lupus erythematosus and vasculitis: Remission, relapse, and re-treatment

Authors

  • K. G. C. Smith,

    Corresponding author
    1. University of Cambridge School of Clinical Medicine, and Addenbrooke's Hospital, Cambridge, UK
    • Cambridge Institute for Medical Research, Box 139, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2XY, UK
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    • Drs. Smith and Jayne have received consulting fees (less than $10,000 each) from Roche (UK) and Novartis.

  • R. B. Jones,

    1. Addenbrooke's Hospital, Cambridge, UK
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  • S. M. Burns,

    1. Addenbrooke's Hospital, Cambridge, UK
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  • D. R. W. Jayne

    1. University of Cambridge School of Clinical Medicine, and Addenbrooke's Hospital, Cambridge, UK
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    • Drs. Smith and Jayne have received consulting fees (less than $10,000 each) from Roche (UK) and Novartis.


Abstract

Objective

Current treatments for systemic lupus erythematosus (SLE) and vasculitis contribute to mortality and incapacity and are only partially effective; thus, newer therapies are clearly needed. Depletion of B cells has led to disease control in patients with autoimmune disorders. We sought to assess the long-term efficacy and safety of a B cell–depleting therapy in patients with SLE and patients with vasculitis.

Methods

In a prospective study with a median followup of 24 months, 11 patients with active or refractory SLE and 11 patients with active or refractory antineutrophil cytoplasmic antibody–associated vasculitis (AAV) received a course of therapy with rituximab (an anti-CD20 monoclonal antibody) along with a single dose of intravenous cyclophosphamide.

Results

Remission followed rapid B cell depletion, with response rates of 100% among the 11 patients with SLE (6 patients had a complete response, and 5 patients had a partial response) and 91% among the 11 patients with AAV (9 patients had a complete response, and 1 patient had partial remission). A renal response occurred in all 6 patients with lupus nephritis. Clinical improvement was accompanied by significant reductions in the daily dose of prednisolone. Relapse occurred in 64% of the patients with SLE and in 60% of those with AAV. B cell return preceded relapse in the majority of patients, and further treatment with rituximab proved effective. IgG and IgM levels were maintained in the normal range. The incidence of infective complications was low; however, infusion reactions were common, and human antichimeric antibodies developed in 5 of 14 patients.

Conclusion

B cell depletion offers the prospect of sustained disease remission and improved disease control combined with low toxicity in patients with active or refractory SLE or AAV. Relapse following treatment is common, but re-treatment is rapidly effective.

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