Efficacy of selective B cell blockade in the treatment of rheumatoid arthritis

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Arthritis Rheum 2002 Aug;46(8):2029-33

Efficacy of selective B cell blockade in the treatment of rheumatoid

arthritis: evidence for a pathogenetic role of B cells.

Vita SD, Zaja F, Sacco S, Candia AD, Fanin R, Ferraccioli G.

University of Udine, Udine, Italy. gf.ferraccioli@...

OBJECTIVE: The pathogenetic role of B cells in rheumatoid arthritis (RA)

is under debate, but it is currently believed to be marginal. The

availability of selective anti-B cell treatment provides a unique

opportunity to clarify this issue. This study was undertaken to

investigate the effects of B cell blockade in the treatment of

refractory RA, and to evaluate the implications with regard to the role

of B cells in the disease. METHODS: Five female patients with active,

evolving erosive RA were treated with rituximab, an anti-CD20 chimeric

monoclonal antibody. All 5 patients had been nonresponders to

combination therapy with methotrexate plus cyclosporin A. Two of the 5

had also failed to respond to anti-tumor necrosis factor alpha therapy.

All of these treatments were discontinued 1 month before institution of

anti-CD20 therapy. RESULTS: Marked clinical improvement was observed in

2 patients (American College of Rheumatology 70% response [ACR70] and

ACR50, respectively), starting at the end of the second month after

institution of anti-CD20 therapy (month 2) and lasting until month 10 in

1 patient (articular relapse) and month 12 in the other (last followup).

ACR20 response was observed in 2 additional patients, lasting until

month 5 and month 7, respectively (articular relapse in both). Decrease

or normalization of serum C-reactive protein and rheumatoid factor

levels were observed in these patients. In contrast, patient 3 had no

response to the treatment. RA synovitis and evolving erosive damage were

decreased in patients exhibiting a major response, as demonstrated by

imaging studies. CONCLUSION: Our finding of the clinical efficacy of

selective B cell blockade indicates that B cells play a critical role in

rheumatoid synovitis, at least in a subset of patients. Qualitative or

quantitative differences in B cell commitment in RA pathobiology might

have a function in the different responses observed.

PMID: 12209504