More positive results with rituximab in RA

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Sep 12, 2002

More positive results with rituximab in RA

Further positive results with rituximab in rheumatoid arthritis (RA) have

been reported, from an Italian study involving 5 patients described in the

August issue of Arthritis & Rheumatism [1]. While these results are not as

dramatic as those reported previously with this drug, they confirm the

experience and provide more direct evidence that B-cell ablative therapy may

have a role in at least a subset of patients with RA, comments an

accompanying editorial [2].

Rituximab, an anti-CD20 monoclonal antibody, acts by depleting B cells.

Already marketed for B-cell malignancies such as non-Hodgkin's lymphoma (as

Rituxan® [Genentech]), it is now being investigated in a variety of

autoimmune disorders. In addition to RA, positive results have also been

reported in systemic lupus erythematosus (SLE), immune thrombocytopenic

purpura (ITP), autoimmune hemolytic anemia, cold agglutinin diseases,

myasthenia gravis, and Wegener's granulomatosis.

The previous study in RA, in which a combination of rituximab with

cyclophosphamide and a corticosteroid produced " highly encouraging results, "

caused quite a stir when it was presented at the 2000 ACR meeting, as

reported by rheumawire. It has subsequently been published in Rheumatology

[3].

Rituximab alone " clinically beneficial "

In the new report, rituximab was used alone and produced a clinical response

in 4 of 5 patients with refractory RA. All of these patients had failed to

respond to a combination of methotrexate and cyclosporin, and 2 had also

failed to respond to anti-TNF therapy, say the authors, Dr Salvatore De Vita

and colleagues at the University of Udine, Italy.

Of the patients, 2 showed a marked clinical improvement (ACR70 and ACR50

responses) that was sustained for 10 months in 1 patient and for at least a

year in the other. Imaging studies showed a marked decrease in RA synovitis

and synovial vascularization and a lack of progression of erosive damage. A

further 2 patients achieved an ACR20 response, lasting for 5 and 7 months

respectively. All 4 patients showed a decrease or normalization of serum

C-reactive protein and rheumatoid factor levels. In contrast, 1 of the 5

patients had no response to treatment.

Rituximab " proved clinically beneficial in 4 of 5 patients with aggressive

and refractory RA, indicating that B cells were critical in sustaining

chronic inflammation and disease activity in such patients, " the researchers

conclude. But they caution that " while our demonstration of the efficacy of

selective B-cell blockade was useful to highlight the biological role of B

cells in rheumatoid synovitis, the clinical impact of anti-CD20 therapy,

alone or in combination, clearly requires additional investigation. "

Benefit in RA was " surprising to many "

The fact that an approach based on ablating B cells is clinically beneficial

in RA has been " surprising to many, " comments Dr Dhavalkumar Patel (Duke

University Medical Center, Durham, NC) in the accompanying editorial [2].

Although B cells are known to play a key role in the pathogenesis of

diseases associated with autoantibodies such as ITP and SLE, their role in

RA has been controversial.

But the data from this new study, taken together with the other results in

RA, have provided " solid evidence for a pathogenic role of B cells in at

least a subset of patients with RA, " the editorial continues. " Thus the

concept that B-cell ablation is a viable therapy in autoimmunity, including

RA, has been established. "

Zosia Chustecka

Cited sources

1. Vita SD, Zaja F, Sacco S, et al. Efficacy of selective B cell blockade in

the treatment of rheumatoid arthritis: evidence for a pathogenetic role of B

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

2. Patel DD. B cell-ablative therapy for the treatment of autoimmune

diseases. Arthritis Rheum 2002 Aug; 46(8):1984-5.

3. JC, Cambridge G. Sustained improvement in rheumatoid arthritis

following a protocol designed to deplete B lymphocytes. Rheumatology

(Oxford) 2001 Feb; 40(2):205-11.