Rituxan Shown to Improve RA Symptoms Over Several Courses, According to Studies' Interim Findings

In November 2006, Genentech, Inc. and Biogen Idec, Inc. announced positive results from recent analyses of ongoing open-label extension studies of Rituxan's effect on patients with rheumatoid arthritis (RA). The leader of these studies is Mark Genovese, M.D., Associate Professor of Medicine, Immunology and Rheumatology, Stanford University Medical Center. The findings thus far, along with data on physical function and mental and physical health measures and a preliminary safety analysis of TNF antagonist use following Rituxan treatment, will be presented at the ACR Annual Scientific Meeting.

Rituxan is the first RA therapy that targets CD20-positive B-cells. While RA has traditionally been considered a T-cell--mediated disease, newer research suggests that other immune cells called B-cells may play multiple roles in the initiation and development of RA. These roles include excessive presentation of substances capable of triggering an immune response, overproduction of antibodies that trigger an immune attack against a person's own cells or tissues, and production of chemical signal molecules (cytokines) known to promote inflammation and joint damage.

The patients used in these studies had specifically not responded well to previous treatment with one or more tumor necrosis factor (TNF) antagonist therapies. The studies, classified as open-label extension studies, were designed to evaluate the long-term efficacy and safety of a subsequent course of Rituxan treatment. 155 patients received Rituxan (1000 mg i.v. infusion on days 1 and 15) in combination with a stable dose of MTX. Patients treated with a first course of Rituxan in a Phase II or Phase III study were eligible to receive additional open-label treatment courses based on physician discretion if they had active disease and a predefined improvement to the first treatment course by week 24. After 16 weeks or more, patients who received placebo in the original studies were also eligible to enter the extension study and receive one or more courses of Rituxan.

These interim findings showed that a greater proportion of patients had a better therapeutic response following treatment with a subsequent course of Rituxan, in combination with methotrexate (MTX), compared to outcomes after their first course. Put differently, the interim data show that patients who received a subsequent course of Rituxan experienced comparable or improved RA symptom relief compared to outcomes after their first course.

However, the rate of serious adverse events (grade 3 or 4) was approximately 11 percent and serious infections occurred in 2 percent of patients. In the past as well, severe infusion reactions have been reported in patients treated with Rituxan, some with fatal outcomes in patients with NHL. These severe reactions typically occur during first infusions. The most severe manifestations include pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, and anaphylactic and anaphylactoid events. Both the companies and the researchers have acknowledged these concerns and have stated it as their conviction to continue to monitor the long-term safety of Rituxan in RA therapy.

Article References
Subsequent Course Of Rituxan Improved Outcomes In Rheumatoid Arthritis Patients Who Inadequately Responded To Tnf Antagonist Therapy, Medical News Today, site accessed on 11/23/2006.