Repeat rituximab safe for rheumatoid arthritis

NEW YORK (Reuters Health) - Additional courses of rituximab in rheumatoid arthritis patients who continue to experience symptoms after they finish an initial course of treatment with this tumor necrosis factor (TNF) inhibitor can induce a sustained and safe clinical response, an international team of researchers reports.

The findings of this study of rituximab, marketed in the U.S. as Rituxan, appear in the journal Arthritis and Rheumatism.

Dr. Edward Keystone of Mt. Sinai Hospital and the University of Toronto, Canada, led an extension study that analyzed rituximab in 1,039 patients who received one or more courses of the drug for active rheumatoid arthritis.

There were 570 patients who received two courses, 190 patients who received three courses and 40 patients who received four courses.

The investigators measured clinical response using the American College of Rheumatology (ACR) criteria for improvement of 20 percent (ACR20), 50 percent (ACR50) or 70 percent (ACR70).

They also used the European League Against Rheumatism (EULAR) response criteria as well as other tests to access response.

Regardless of which TNF inhibitor the patient was previously expose to, the ACR20 responses were comparable after course one and after course two (65 percent versus 72 percent), as were ACR50 and ACR70 responses," Dr. Keystone and colleagues report.

A EULAR response of moderate-to-good was more frequently seen with repeated courses of rituximab. There was a response rate of 88 percent after a second course of the TNF inhibitor compared with a 79 percent response after an initial course of treatment.

EULAR remission occurred in twice as many patients after a second course, taking place in 13 percent compared with a complete response in only 6 percent after a single course of treatment.

The most common adverse events were mild-to-moderate acute infusion-related events, which decreased with each course of treatment. The frequency of serious infections, occurring at a rate of 5.1 cases per 100 patients per year, did not increase with repeated courses of treatment.

Blood levels of the immune cells IgM and IgG declined with each course of rituximab, but serious infection rates did not increase. The rate of serious infections per 100 patients per year was about 5 for patients with low IgM levels, low IgG levels, and for those who maintains level in the normal range.

Repeated rituximab courses seem to result in "consistent and sustained" effectiveness compared with the original course, without causing new adverse events in patients who have not taken TNF inhibitors before or in patients who previously did not response to these drugs, the researchers conclude.

SOURCE: Arthritis and Rheumatism, December 2007.