RESEARCH - Assessment of rituximab's immunomodulatory synovial effects: ARISE trial

[Guest guest]

Ann Rheum Dis. 2008 Mar;67(3):402-8. Epub 2007 Jul 20.

Assessment of rituximab's immunomodulatory synovial effects (ARISE

trial). 1: clinical and synovial biomarker results.

Kavanaugh A, Rosengren S, Lee SJ, Hammaker D, Firestein GS, Kalunian

K, Wei N, Boyle DL.

University of California, San Diego, Division of Rheumatology,

Allergy, and Immunology, 9500 Gilman Drive, Mail Code 0943, La Jolla,

CA 92093-0943, USA.

OBJECTIVE: Treatment with the anti-CD20 monoclonal antibody (mAb)

rituximab is effective in rheumatoid arthritis (RA). Marked depletion

of circulating B cells, seen in almost all patients, does not

correlate with efficacy. The potential synovial immunomodulatory

effects of rituximab have not been fully defined. METHODS: The ARISE

trial is an open label, serial synovial biopsy (pre-treatment and 8

weeks) study of rituximab, given 1 g intravenously on days 0 and 14

without peri-infusional steroids, in active RA patients on concomitant

methotrexate (MTX). Synovial tissue was analysed by

immunohistochemistry with digital image analysis and gene expression

by real-time PCR. RESULTS: The mean (SD) baseline DAS28 score was 6.5

(0.4), and mean MTX dose 17.3 mg/week. Of 13 patients, 11 had failed

prior tumour necrosis factor (TNF) inhibitor therapy. With treatment,

all patients experienced near complete depletion of circulating B cell

numbers. During the 6 months after treatment, 7/13 patients achieved

an American College of Rheumatology (ACR) 20% improvement (ACR20)

response, 3/13 an ACR50 response and 2/13 an ACR70 response. There was

a significant decrease in synovial B cells after treatment, but only a

small trend towards greater reduction among clinical responders. Among

the three patients with ACR50 responses there was a significant

decrease in synovial immunoglobulin synthesis.

CONCLUSIONS: These data suggest that unlike those in circulation,

synovial B cells are decreased but are not eliminated by rituximab

therapy. Patients with higher levels of response may have more

consistent depletion of synovial B cells, and may also have an

alteration in synovial B cell function, as indicated by decreases in

synovial immunoglobulin synthesis. Thus, effects on synovial B cells

may be necessary but not sufficient for inducing clinical efficacy.

Other effects, such as on primary lymph organ B cell antigen

presentation or cytokine production, may be operative.

PMID: 176445

http://www.ncbi.nlm.nih.gov/pubmed/17644541

--

Not an MD