The US Food and Drug Administration (FDA) has approved the anti-CD20+ B-cell-targeted monoclonal antibody rituximab (Rituxan®) in combination with methotrexate (MTX) for adult patients with moderate to severe rheumatoid arthritis (RA) who experienced an inadequate response to one or more tumor necrosis factor (TNF) antagonists. The newly approved agent has an established therapeutic record in the treatment of non-Hodgkin's lymphoma.

Significant step forward for TNF-refractory patients

"This is a significant step for patients who have had an inadequate response to anti-TNF agents," says Philip J. Mease, MD, of the department of internal medicine at the Swedish Medical Center and Rheumatology Associates in Seattle, Washington. "At least initially, the approval is specifically designed [for such patients], and so we have a number of patients [on whom] we will use it for that reason.

"[Rituximab] also represents a very novel approach from a biologic mechanism point of view. It really addresses the fact that the B cell is an important player that acts as a traffic cop in the process of inflammation in autoimmune disease," says Dr. Mease, who predicts that there will be some competition with abatacept (Orencia®), the co-stimulation modulator of T-cell activation that received FDA approval in January. Although abatacept is not yet commercially available, Dr. Mease says that it will be used for the anti-TNF failure population along with rituximab.

Rituximab provides an important treatment option to improve the quality of life of people with RA, says John H. Klippel, MD, president and CEO of the Arthritis Foundation in Atlanta, Georgia, in a written statement from the Arthritis Foundation.1 "Enormous progress has been made in the treatment of RA over the past decade; however, many patients cannot tolerate or do not respond adequately to the anti-TNF agents that are currently available. Rituximab expands the treatment options for these patients."

REFLEX study used as basis for FDA approval

FDA approval was based on results from the 24-week Randomized Evaluation of Long-Term Efficacy of Rituximab in RA (REFLEX) phase III trial.2 In this study, 520 patients whose RA failed to respond to an average of 2.5 disease-modifying antirheumatic drugs (DMARDs; exclusive of MTX) and 1.5 anti-TNF agents received either a single treatment course of two intravenous infusions of rituximab (1000 mg on days 1 and 15) with a stable dose of MTX or placebo with a stable dose of MTX. The ritixumab group was more likely to achieve American College of Rheumatology (ACR) 20, 50, and 70 response rates compared to patients receiving placebo and MTX (P <.0001 in all categories). In addition, patients receiving rituximab also displayed clinically and statistically significant changes in Disease Activity Score (DAS28) as well as EULAR response.

The most frequently reported adverse events that occurred with rituximab in the REFLEX trial were primarily infusion-associated. Serious adverse events occurred in 7% of patients receiving rituximab and MTX compared to 10% in patients receiving placebo and MTX. Less than 1% of acute infusion reactions were serious, the study showed. The incidence of serious infections was low in both the rituximab and placebo groups (2% and 1%, respectively).


References

  1. Arthritis Foundation Statement on Rituximab for Rheumatoid Arthritis [press release]. Atlanta, Ga: The Arthritis Foundation; March 1, 2006. 
  2. Cohen SB, Greenwald M, Dougados MR, et al. Efficacy and safety of rituximab in active RA patients who experienced an inadequate response to one or more anti-TNF-α therapies (REFLEX study). Presented at: 69th Annual Meeting of the American College of Rheumatology; November 12–17, 2005; San Diego, Calif. Abstract 1830.