Rituximab, a biologic agent that selectively depletes B cells, has been successfully used to treat non-Hodgkin's lymphoma. It has also been shown to improve disease symptoms for RA patients, when injected at aggressive levels for a two-week period. To investigate this biologic's potential long-term therapeutic value, an international team of scientists set out to compare the effectiveness and safety of different rituximab doses over a 24-week period, with and without steroids. Their study focused on 465 RA patients with moderate to severe symptoms resistant to disease-modifying antirheumatic drugs (DMARDs), including other biologics. The results, featured in the May 2006 issue of Arthritis & Rheumatism (http://www.
Drawn from outpatient populations in California, Texas, Arizona, Switzerland, Sweden, Poland, and England, the subjects were randomly divided into nine treatment groups. Three groups received a 1,000 mg. dose of rituximab--two infusions two weeks apart--with either intravenous steroid, oral steroid, or placebo. Three groups received a 500 mg. dose of rituximab--two infusions two weeks apart--with either intravenous steroid, oral steroid, or placebo. Three groups received a placebo with either intravenous steroid, oral steroid, or another placebo. All subjects received the DMARD methotrexate (MXT). All subjects were evaluated every four weeks for changes in the Disease Active Score (DAS), a 28-joint assessment for swelling and tenderness, as well as for overall disease improvement, with the goal of meeting the American College of Rheumatology (ACR) 20 percent improvement criteria.
At the 24-week culmination, 54 percent of the subjects in three rituximab 1,000 mg. X 2 groups and 55 percent of the subjects in the three rituximab 500 mg. X 2 groups had achieved the desired ACR20 response, compared with 28 percent of the subjects in the three placebo groups. The different dosages of rituximab did not have a statistically significant impact on the odds of achieving an ACR20 response, and analyses of the proportions of patients who achieved higher ACR improvement scores--50 percent and 70 percent--showed similar patterns. Changes in DAS28 at week 24 reflected the ACR response findings, as did the subjects reports of relief from joint pain and stiffness. What's more, subjects in the rituximab groups showed gains toward disease remission earlier in the course of treatment than subjects in the placebo group.
Steroids, whether received intravenously or orally, showed no significant correlation with disease improvement scores among the rituximab groups. Intravenous steroid, however, showed a positive correlation to improved tolerability during the first rituximab infusion in both dosage groups. Overall, adverse events associated with rituximab were mild and easily managed. Headache was the most common complaint.
Confirming the role of B cells in the inflammatory processes behind RA, this study demonstrates the effectiveness and safety of a unique biologic therapy, in moderate doses and independent of steroids. Yet, as its leading author, Dr. Paul Emery, notes, further studies are needed before applying the results to the routine treatment of RA patients. "Both doses of rituximab explored in this study warrant further differential exploration and longer-term followup," he stresses.
Article: "The Efficacy and Safety of Rituximab in Patients With Active Rheumatoid Arthritis: The Results of a Phase IIb Double-Blind, Placebo-Controlled, Dose-Ranging Trial," Paul Emery, Roy Fleischmann, Anna Filipowicz-Sosnowska, Joy Schechtman, Leszek Szczepanski, Arthur Kavanaugh, Artur J. Racewicz, Ronald F. van Vollenhoven, Nicole F. Li, Sunil Argarwal, Eva W. Hessey, and Timothy M. Shaw, for the Dose-Ranging Assessment: International Clinical Evaluation of Rituximab in Rheumatoid Arthritis (DANCER) Study Group, Arthritis & Rheumatism, May 2006, 54:5, pp. 1390-1400.