More positive results with rituximab in RA

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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].

Separately, the UK researchers who first reported dramatic benefit in RA

with rituximab (when used in combination with cyclophosphamide and

corticosteroid) have published further details on 22 patients in the October

issue of the ls of Rheumatic Diseases [3]. This group presented

preliminary findings at the 2000 ACR meeting, as reported by rheumawire.

Another paper (also in ls of Rheumatic Diseases) describes the case

reports of 3 patients with refractory systemic antibody-mediated autoimmune

diseases (cryoglobulinemia, Goodpasture's syndrome, and vasculitis), in whom

rituximab resolved all clinical and laboratory manifestations [4].

From these reports and previously published data, " it appears that rituximab

treatment of autoimmune diseases is safe and shows enough promise to justify

continued study, " concludes an accompanying editorial [5].

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

previously been reported in systemic lupus erythematosus (SLE), immune

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

diseases, myasthenia gravis, and Wegener's granulomatosis.

Rituximab alone " clinically beneficial "

In the new report of benefit in RA [1], rituximab was used alone and

produced a clinical response in 4 of 5 patients with refractory disease. 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. "