RESEARCH - A dose-escalation study of rituximab for SLE and ' syndrome: immunological analysis of B cells, T cells, and cytokines

[Guest guest]

Rheumatology Advance Access published online on April 8, 2008

Rheumatology, doi:10.1093/rheumatology/ken071

A dose-escalation study of rituximab for treatment of systemic lupus

erythematosus and ' syndrome: immunological analysis of B cells,

T cells and cytokines

Y. Tamimoto1, T. Horiuchi1, H. Tsukamoto1, J. Otsuka1,2, H. Mitoma1,

Y. Kimoto1, H. Nakashima1, K. Muta3, Y. Abe3, C. Kiyohara4, A. Ueda5,

K. Nagasawa6, S. Yoshizawa7, T. Shimoda7 and M. Harada1

1Department of Medicine and Biosystemic Science, Kyushu University,

Fukuoka, 2National Hospital Organization Kinki-Chuo Chest Medical

Center, Sakai, 3Department of Medicine and Bioregulatory Science,

4Department of Preventive Medicine, Graduate School of Medical

Sciences, Kyushu University, Fukuoka, 5Miyazaki Prefectural Miyazaki

Hospital, Miyazaki, 6Department of Internal Medicine, Saga University,

Saga and 7National Hospital Organization Fukuoka Hospital, Fukuoka,

Japan.

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 ' 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 ' 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- 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.

http://rheumatology.oxfordjournals.org/cgi/content/abstract/ken071v1?papetoc

--

Not an MD