my personal edition > rheumatoid arthritis > news


  E-Mail this DGDispatch to a colleague

DGDispatch

Treatment-Resistant Rheumatoid Arthritis May Respond to Rituximab Combined With Methotrexate: Presented at EULAR

By Paula Moyer

VIENNA, AUSTRIA -- June 10, 2005 -- Treatment-resistant rheumatoid arthritis (RA) may respond to rituximab (Rituxan), a B-cell-depleting agent used in the treatment of non-Hodgkin's lymphoma, according to research presented here June 9^th at EULAR 2005, the European Congress of Rheumatology.

The results hold promise for patients who live with active RA despite treatment with either methotrexate or with the antitumor necrosis factor (anti-TNF) agents currently approved to treat RA.

The phase 2b Dose-ranging Assessment iNternational Clinical Evaluation of Rituximab in RA (DANCER) trial showed that rituximab may be effective because it targets B cells, key players in the onset and progression of RA.

"Rituximab works better than placebo at both doses that we studied in the trial," said principal investigator Paul Emery, MD, professor of medicine, department of rheumatology, University of Leeds, Leeds, United Kingdom. "Over 25% of these patients had had anti-TNF treatment with no response," Dr. Emery said.

Earlier research showed that rituximab combined with methotrexate is more effective than rituximab alone.

In their study, the DANCER investigators wanted to identify the therapeutic dose of rituximab to use with methotrexate in patients whose disease was active despite treatment with methotrexate or with anti-TNF agents. They also wanted to assess the role of glucocorticoids, which are conventionally used alongside rituximab to prevent infusion reactions in patients with non-Hodgkin's lymphoma.

They randomized the 465 patients to placebo or rituximab 500 mg or 1,000 mg on days 1 and 15. On those days, patients also underwent 1 of 3 glucocorticoid treatments: placebo, IV methylprednisolone 200 mg, or IV methylprednisolone 200 mg plus oral prednisone 60 mg/day on days 2 through 7, tapering to 30 mg daily on days 8 through 14. Patients continued on methotrexate if they were already receiving it, typically at a dose of 10 to 25 mg per week.

At the beginning of the study, the average number of swollen and tender joints was 21 and 33 respectively, and patients had a mean disease activity score of 6.8. They were taking an average of 15.5 mg of methotrexate per week and had rheumatoid arthritis for an average of 10.4 years. The mean number of disease-modifying antirheumatic drugs (DMARDs) per patient was 2.4, and 32% had received prior treatment with an anti-TNF agent.

At week 24 of the study, 35% of subjects in the placebo group had dropped out, compared with 9% in the 500-mg rituximab group and 14% of 1,000-mg rituximab group. Most discontinuations were due to lack of effect, Dr. Emery said. No patients on placebo dropped out due to adverse events, while 1.6% of those in the 500-mg group and 3.1% of the 1,000-mg group did.

Treatment was evaluated according to success in achieving a 20% decrease in symptoms according to American College of Rheumatology (ACR20) criteria, a 50% decrease in symptoms (ACR50), and a 70% decrease (ACR70).

Patients on rituximab had a "highly significant response," Dr. Emery said. Among the 367 evaluable patients at week 24, ACR20 rates were 54% for those in the 1,000-mg group, 55% for those in the 500-mg group, and 28% for those on placebo (P <.0001).

At higher thresholds, 34% of those in the 1,000-mg group had an ACR50 response, as did 33% of those in the 500-mg group, and 13% of those in the placebo group (P <.0001). The respectively ACR70 rates were 20%, 13% and 5% (P <.05).

Mean Disease Activity Score (DAS) was 2.05 points lower in the 1,000-mg group compared with baseline, 1.79 points lower in the 500-mg group, and 0.67 points lower in the placebo group (P <.0001 for both treatment arms).

Glucocorticoids were linked to no significant increase in efficacy, although fewer patients treated with glucocorticoids had infusion reactions, which were the most common adverse events and occurred more commonly during the first infusion.

Serious adverse events occurred in 6.8%, 7.3%, and 2.7%, respectively, and consisted primarily of respiratory infections. Dr. Emery said that, although treatment with rituximab is "surprisingly safe," the long-term implications of treating rheumatoid arthritis with a B-cell-depleting agent are unknown.

Rituxan is manufactured by Roche, which funded the study.


[Presentation title: Primary Analysis of a Double-Blind, Placebo-Controlled, Dose-Ranging Trial of Rituximab, an Anti-CD20 Monoclonal Antibody, in Patients With Rheumatoid Arthritis Receiving Methotrexate (DANCER trial). Abstract OP0008]

E-Mail this DGDispatch to a colleague

To print, use this version