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Assessment of rituximab’s immunomodulatory synovial effects (ARISE trial). 1: clinical and synovial biomarker results

¹ University of California, San Diego, Division of Rheumatology, Allergy, and Immunology, La Jolla, California, USA
² Arthritis and Osteoporosis Center of Maryland, Fredericksburg, Maryland, USA

Correspondence to:
A Kavanaugh, University of California, San Diego, Division of Rheumatology, Allergy, and Immunology, 9500 Gilman Drive, Mail Code 0943, La Jolla, CA 92093-0943, USA; akavanaugh{at}ucsd.edu

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.

This article has been cited by other articles:

				R M Thurlings, K Vos, C A Wijbrandts, A H Zwinderman, D M Gerlag, and P P Tak Synovial tissue response to rituximab: mechanism of action and identification of biomarkers of response Ann Rheum Dis, July 1, 2008; 67(7): 917 - 925. [Abstract] [Full Text] [PDF]