Both groups were evaluated when they started the second therapy and again six months later. Improvements in one subgroup were measured using the Disease Activity Score, or DAS28, an assessment based on 28 tender and swollen joints. Improvements in the second subgroup were measured using the Health Assessment Questionnaire, or HAQ, a patient-reported measure of physical function and disability levels.

In the group with DAS28 scores, 54.8 percent of those who took rituximab reported a “good” or “moderate” response (according to the European League Against Rheumatism criteria) six months after they had switched, compared to 47.3 percent of those who took a second anti-TNF. In the group with HAQ scores, 38.4 percent on rituximab reported they experienced a clinically important improvement compared to 29.6 percent in the anti-TNF group. In both subgroups, the differences in improvement between the rituximab and the anti-TNF groups were considered statistically significant.

“We are continuing to learn about the nature of inflammation in rheumatoid arthritis, and for some patients it may be better to try to block their inflammation using rituximab, which inhibits B-cells, as opposed to anti-TNF therapies, which block the cytokine tumor necrosis factor, which is an important protein involved in inflammation,” says Dr. Hyrich. This research builds on a previous, smaller study that found similar results when rituximab was used as a second-line therapy, he added.

But there is still much to learn. She says researchers are still trying to understand why some patients respond better to one drug than another. “I don't think we fully understand the way in which rituximab is controlling symptoms in rheumatoid arthritis. There is some evidence that patients who are positive for rheumatoid factor or anti-CCP antibodies will respond better to rituximab compared to those who are negative for these antibodies,” she says. “In other patients, TNF may be less important in their inflammation and other proteins or cells more important.”

Dr. Hyrich says the most important thing patients should do is discuss their individual treatment options with their rheumatologist.

Daniel E. Furst, MD, the Carl M. Pearson Professor of Rheumatology at UCLA Medical Center, believes some imbalances may exist in the patient groups in this study because patients were not randomly assigned a second biologic. That could have biased the results to favor rituximab, he says. For example, among the DAS28 group, nearly 60 percent of patients who switched to a second anti-TNF stopped the first one because of inefficacy. “If that group stopped because of primary inefficacy – rather than for loss of response or adverse event – one wouldn’t expect the second [anti-TNF] to work, but they switched to the [anti-TNF] anyway,” Dr. Furst explains. “There’s a chance these [results] were biased because of the reasons patients switched.”

Dr. Furst, who was one of the lead authors of the ACR’s revised guidelines for DMARD therapy, believes one must understand why a patient failed the first anti-TNF to get a sense of how well he or she will do with the medication they try next. That’s what he and his colleagues tried to keep in mind when they were revising the guidelines, thus allowing for greater flexibility and choice, he says.

The updated guidelines recommend that patients who have no response or an inadequate response to an anti-TNF after three months try either a second anti-TNF or a different type of biologic. If a patient experienced a serious adverse event, the guidelines recommend switching to a biologic that isn’t an anti-TNF.

“If the patient ‘failed’ because they had absolutely no response, it makes good sense to try a drug like Rituxan or another non-TNF biologic,” Dr. Furst says. “This approach is supported by the medical literature.”

Robert Katz, MD, professor of medicine at Rush University Medical Center in Chicago, says patients should also keep in mind practical considerations when making a switch to a second biologic. “There could be problems regarding insurance, method of administration [infusion vs. injection], and doctor preference and the location of infusion facilities that could also influence this decision,” he says.

Dr. Hyrich says the British Society for Rheumatology receives funding from a number of pharmaceutical companies including Abbott, Amgen, Roche, Schering-Plough, and Wyeth. But she says all decisions regarding analysis and publication were independent from pharmaceutical funding.