“This disease is a chronically relapsing disease and cyclophosphamide has been effective in the past. But if you have to be exposed to cyclophosphamide repeatedly over a disease span that goes for many, many years, you accumulate a significant dose exposure,” says Dr. Specks. “And with an increased dose exposure comes a substantially increased risk of bladder cancer and other cancers. Rituximab is an alternative agent not associated with this risk and that represents a significant advance for patients.”

A disadvantage of rituximab is likely to be cost, as biologics are generally much more expensive than older immunosuppressive drugs.

Rheumatologist Teresa K. Tarrant, MD, an assistant professor of medicine at the Thurston Arthritis Research Center and University of North Carolina School of Medicine in Chapel Hill, says that by following patients in this study for a longer period of time, researchers are able to offer important information about remission and disease relapse with respect to the two different treatment strategies. But she says that because safety data was similar in both groups, this study does not guide doctors and patients to which treatments are better for which patients.

“The trial does provide meaningful, more long-term data about an additional therapeutic approach for [AAV] patients that compares favorably to standard therapy,” Dr. Tarrant says. But she also notes that, “the most severely ill patients with [AAV] were excluded from the trial, so there is still limited information in how best to treat these patients.”  

Dr. Specks says the next phase of research will look at remission maintenance. “We don’t quite know which patients will ultimately relapse after rituximab or which patients will not relapse. We don’t have good biomarkers for that,” he explains.

Dr. Tarrant agrees this is an important area of focus going forward. “Larger and longer studies are still needed to answer questions about which patients, if any, may better respond to rituximab or cyclophosphamide and azathioprine,” she says. “Many patients achieved remission, but over half had a recurrence of their disease at 18 months. It will be important to study treatments in relapsed patients to see if repeated doses of rituximab are as successful.”

The study was funded in part by the Immune Tolerance Network, a research consortium sponsored by the National Institute of Allergy and Infectious Diseases, which is part of the National Institutes of Health, as well as Genentech and Biogen Idec, the maker of rituximab.