Drug regarded as alternative to standard treatment for preventing relapse of certain type of vasculitis does not appear as effective

"Relapses of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) occur in 50 percent of patients within 5 years of diagnosis, and treatment toxicity is common. Safe and effective therapies to maintain remission of AAV are a priority," the authors write. "In AAV, small observational studies and randomized controlled trials reported successful remission induction and remission maintenance with mycophenolate mofetil. Whether mycophenolate mofetil is more effective than azathioprine [an immunosuppressive] for preventing relapses in AAV is uncertain."

Thomas F. Hiemstra, M.D., M.R.C.P., of the University of Cambridge and Lupus and Vasculitis Unit, Addenbrookes Hospital, Cambridge, England, and colleagues examined whether mycophenolate mofetil reduces the risk of relapse compared with azathioprine in patients with AAV in remission, and compared the risk of serious adverse events between treatment groups. The randomized trial was conducted at 42 centers in 11 European countries between April 2002 and January 2009. Eligible patients had newly diagnosed AAV and were ages 18 to 75 years at diagnosis. Patients were randomly assigned to receive azathioprine or mycophenolate mofetil after induction of remission with the agents cyclophosphamide and prednisolone.

A total of 156 patients were assigned to azathioprine (n = 80) or mycophenolate mofetil (n = 76) and were followed up for a median (midpoint) of 39 months. The researchers found that relapses were more common in the mycophenolate mofetil group (42/76 patients; 18 with major and 24 with minor relapses) compared with the azathioprine group (30/80 patients; 10 with major and 20 with minor relapses).

Severe adverse events did not differ significantly between groups, with 22 severe adverse events in 13 patients (16 percent) in the azathioprine group and 8 severe adverse events in 8 patients (7.5 percent) in the mycophenolate mofetil group. There were 8 severe infections in 8 patients in the azathioprine group and 3 severe infections in 3 patients in the mycophenolate mofetil group.

The secondary outcomes of Vasculitis Damage Index, estimated glomerular filtration rate (a measure of kidney function), and proteinuria (the presence of excessive protein in the urine) did not differ significantly between groups.

"Although mycophenolate mofetil is frequently regarded as a potent alternative to azathioprine, we found no evidence to support its use as the initial remission maintenance therapy for patients with AAV," the authors write.

Editorial: Therapeutic Interventions for Systemic Vasculitis

In an accompanying editorial, Gary S. Hoffman, M.D., M.S., of the Cleveland Clinic, Lerner College of Medicine, Case Western Reserve University, Cleveland, writes that at this time, several key therapeutic findings regarding vasculitis research are apparent.

"Remission maintenance therapies (methotrexate, azathioprine) are as effective as prolonged cyclophosphamide and are much safer. Mycophenolate mofetil is associated with a higher relapse rate than azathioprine. Discontinuation of maintenance therapies appears to be associated with a higher rate of relapse than continuation of treatment. However, the risk-benefit formulas of long-term maintenance therapy vs. discontinuation and treatment of relapses require further study. Ideally these questions can be addressed by clinical trials of similar quality and importance as the report by Hiemstra et al and other major contributions of the European Vasculitis Study Group."