A dose-escalation study of rituximab for treatment of systemic lupus erythematosus and Evans' syndrome: Immunological analysis of B cells, T cells and cytokines

Y. Tamimoto, T. Horiuchi, H. Tsukamoto, J. Otsuka, H. Mitoma, Y. Kimoto, H. Nakashima, K. Muta, Y. Abe, C. Kiyohara, A. Ueda, K. Nagasawa, S. Yoshizawa, T. Shimoda, M. Harada

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46 Citations (Scopus)

Abstract

Objective. Accumulating evidence suggests that B-cell depletion therapy by rituximab may be effective for autoimmune disorders. However, an optimal dose of rituximab and a mechanism of its action remain to be established. We performed a dose-escalation study for treatment of Japanese patients with autoimmune diseases including eight with SLE and one with Evans' syndrome. Methods. Rituximab was infused intravenously, weekly 4 times in a dose-escalating fashion at three different doses of 100, 250 or 375 mg/m2 to three patients each. Immunological parameters were monitored at certain points until 12 months after the treatment. Results. Rituximab was well tolerated and safe in these patients. Seven out of eight SLE patients and one with Evans' syndrome clinically responded completely or partially to the treatment. Four patients achieved long-term remission (18-30 months) without any additional treatment. In these patients, a significant decrease in circulating B cells continued for 6 months after the treatment. The mean fluorescence intensities of CD19, CD21, CD40 and BR3 on the residual B cells as well as the percentage of CD69+ CD4+ T cells decreased significantly. Serum TNF-α levels decreased significantly on day 2. The Th1/Th2 balance of CD4+ T cells gradually shifted towards a Th1 type by 6 months. Conclusion. In addition to B-cell depletion, modification of B-cell and T-cell phenotypes as well as cytokine profiles may be involved in the action of rituximab.

Original languageEnglish
Pages (from-to)821-827
Number of pages7
JournalRheumatology
Volume47
Issue number6
DOIs
Publication statusPublished - Jun 2008

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Pharmacology (medical)

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