VIENNA, Austria - New results from an ongoing trial and the primary analysis of the DANCER (Dose-Ranging Assessment iNternational Clinical Evaluation of Rituximab in RA) trial1 are providing evidence for the effectiveness of B-cell depletion using the anti-CD monoclonal antibody rituximab in the treatment of rheumatoid arthritis (RA).

"I think rituximab is a very promising therapy [for RA], mostly for refractory patients, because I don't think we want to deplete B cells if we don't have to," says Vibeke Strand, MD, clinical professor of medicine in the division of immunology at the Stanford University School of Medicine in Palo Alto, California.

This optimism is derived, in part, from the favorable results observed in patients participating in the DANCER trial, presented Thursday at the 6th Annual European Congress of Rheumatology of the European League Against Rheumatism (EULAR) here. This study followed 465 patients who were randomly assigned to nine treatment arms, with randomization stratified by region and rheumatoid factor (RF) status. Placebo or rituximab (either 500 mg or 1000 mg) was given on days 1 and 15 along with one of three glucocorticoid regimens. All patients were using ongoing methotrexate (MTX), and at least one prior DMARD or biologic other than MTX, with 32% having experience with biologic therapy.

Analysis at week 24 of an intent-to-treat subpopulation of 367 RF-positive subjects revealed that 28%, 55%, and 54% of patients given those given placebo, 1 g, or 2 g of rituximab, respectively, achieved the primary endpoint of an ACR20 response.1 Furthermore, 13%, 33%, and 34% had achieved an ACR50 response, and 5%, 13%, and 20% had achieved an ACR70 response.

"It's the biggest study to date which confirms the efficacy [of rituximab] in a difficult group of patients," says Paul Emery, MD, lead author of the DANCER trial and professor of rheumatology at the University of Leeds in Leeds, UK. "We showed a really good response in both groups, but there was a slightly greater response at the higher dose"

The results suggest a potential treatment strategy for physicians using rituximab in RA. "We showed a good response in both groups, but there was a slightly greater response at the higher dose," Josef Smolen, MD, professor of medicine and chairman of the division of rheumatology at the Medical University of Vienna in Austria, tells CIAOMed. "This suggests that doctors can start with a low dose first and then move to a higher dose if they do not get a good response."

Dr. Emery adds that rituximab may also play a role in early RA. "If it is this effective late in the disease, it would be even more effective if given earlier," he says.

While coadministration of steroids did prevent the occurrence of infusion reactions, the most common adverse event, the analysis also revealed that steroid use was not a significant factor in therapeutic response level. "That's very important, because it says that you don't need to use steroids with rituximab, and we already know that rituximab with methotrexate has the most prolonged effect," Dr. Strand says.

 

2-year analysis of rituximab/MTX combination

Indeed, a 2-year analysis of an ongoing Phase IIa study presented here by Dr. Strand and colleagues2 demonstrates that one course of rituximab in patients receiving MTX has beneficial effects that outlast patients receiving placebo, rituximab monotherapy, or concomitant therapy with cyclophosphamide. At 2 years, 47% of patients had not withdrawn from the study for retreatment with rituximab.

Dr. Strand points out that patient-reported physical function appears to be the best measures of responsiveness. "Sustained improvement in HAQ DI [Health Assessment Questionnaire Disability Index] predicts the long responses, and the HAQ DI actually best differentiates between active and placebo therapy."

Despite initial enthusiasm about B-cell depletion therapy for RA, Dr. Smolen, also the chairman of this week's EULAR Congress, says that more careful study has tempered expectations somewhat. "The talk has been tapered from cure to long-term remission," he notes, adding that "some patients from the initial studies are still in remission after 2 years and only taking methotrexate. Rituximab does work. It's an important drug."

References:

  1. Emery P, Li N, Van Vollenhoven R, et al. 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). Presented at: Annual European Congress of Rheumatology of EULAR; June 8-11, 2005; Vienna, Austria. Abstract OP0008.
  2. Strand V, Balbir-Gurman A, Pavelka K, et al. Two-year improvements in physical function reflect sustained benefit in rheumatoid arthritis patients receiving a single course of rituximab with methotrexate. Presented at: Annual European Congress of Rheumatology of EULAR; June 8-11, 2005; Vienna, Austria. Abstract THU0329.