Preliminary results from a large randomized clinical trial of Rituximab ( Rituxan ) in rheumatoid arthritis showed that a greater proportion of patients treated with a single course of Rituximab, with a stable dose of Methotrexate, achieved American College of Rheumatology ( ACR ) 20, 50 and 70 response rates compared to placebo.
The improvement in response rates was shown to be independent of corticosteroids.

The Phase IIb trial included 465 patients who were inadequately responding to Methotrexate and who had failed prior treatment with one or more disease-modifying anti-rheumatic drugs ( DMARDs ), including biologics.

The study, known as DANCER ( Dose-Ranging Assessment International Clinical Evaluation of Rituximab in Rheumatoid Arthritis ), evaluated the efficacy and safety of two doses of Rituximab in combination with Methotrexate, and explored the role of corticosteroids.

Patients, randomized into one of nine treatment arms, received a stable dose of Methotrexate and varying doses of Rituximab and corticosteroids.

Regardless of dose, the DANCER results indicated that Rituximab provided clinically and statistically significant improvement in rheumatoid arthritis symptoms compared to placebo.
In the two Rituximab groups, 54 percent and 55 percent achieved ACR 20; 33 percent and 34 percent achieved ACR 50; and 13 percent and 20 percent achieved ACR 70 – compared to 28 percent, 13 percent and 5 percent for placebo respectively.

" The results of the DANCER study, which evaluated the efficacy and safety of Rituxan in a difficult-to-treat patient population, further validate selective B-cell depletion as a potentially new and viable approach to the treatment of rheumatoid arthritis,” said Roy Fleischmann, of the University of Texas Southwestern Medical Center. “ For the first time, these data also showed that the benefits of Rituxan were independent of short-course corticosteroids, which were given in all previous Rituxan rheumatoid arthritis trials”

The data did not reveal any unexpected safety signals. The most frequently reported adverse events in the study were primarily infusion-related and mild-to-moderate in intensity, including headache, nausea and rigors. Intravenous corticosteroid pre-medication appeared to reduce the incidence and severity of first infusion reactions. Oral corticosteroids did not appear to provide any additional safety benefit.

The reported rate of serious adverse events was higher in the Rituxan groups, but similar to those seen in previous studies of Rituxan in rheumatoid arthritis.
Across the Rituxan groups, 35 percent of patients experienced infections, compared to 28 percent of placebo patients. However, the type and severity of infections were similar between both Rituxan doses and the placebo regimen.
The rate of serious infections was low and was similar across the treatment groups.
In addition, Rituxan therapy had no significant impact on immunoglobulin levels or acquired immunity.

Although there was a trend toward higher ACR 70 responses for patients in one of the Rituxan groups, it was not statistically significant.
Based on the DANCER results, the researchers are planning to evaluate two doses of Rituxan in a Phase III study of patients who are inadequately responding to Methotrexate and who have failed prior treatment with one or more DMARDs.

The primary endpoint of DANCER was ACR 20 response at 24 weeks in rheumatoid factor positive patients ( n=367 ).
Both rheumatoid factor positive and rheumatoid factor negative patients were included in the safety analysis. Of the patients enrolled, 29 percent ( 134/465 ) had inadequately responded to anti-TNF treatments.

Rituximab is a therapeutic antibody that targets and selectively depletes CD20 positive B cells without targeting stem cells or existing plasma cells. B cells may play multiple roles in the pathophysiology of rheumatoid arthtitis.

Source: Annual European Congress of Rheumatology, EULAR 2005


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