Mycophenolate mofetil was more effective than azathioprine in maintaining renal response and preventing relapse in patients with active lupus nephritis, judging from the findings of a phase III clinical trial reported in the Nov. 17 issue of the New England Journal of Medicine.
Compared with azathioprine maintenance therapy, the use of mycophenolate mofetil prolonged the time to treatment failure, which was the study’s primary end point. It also extended the interval until individual components of this end point were reached, including a renal flare, the need for rescue therapy, sustained doubling time of the serum creatinine level, and the development of end-stage renal disease (ESRD), said Dr. Mary Anne Dooley of the University of North Carolina at Chapel Hill and her associates in the manufacturer-sponsored Aspreva Lupus Management Study (ALMS).
The investigators previously reported the results of the induction phase of ALMS, in which the efficacy and safety of mycophenolate mofetil were compared with that of intravenous cyclophosphamide as induction therapy for lupus nephritis. This latest report covers the results of the 3-year maintenance phase of ALMS, a prospective, double-blind trial comparing oral mycophenolate mofetil against oral azathioprine for maintenance of remission among the study subjects who responded to either induction therapy.
The 227 study subjects were aged 12-75 years at baseline and had class III, IV, or V lupus nephritis. They were enrolled at medical centers in Asia, Latin America, North America, Europe, South Africa, and Australia and were randomly assigned to receive mycophenolate mofetil (116 patients) or azathioprine (111 patients).
A total of 127 subjects (55.9% of the mycophenolate group and 48.6% of the azathioprine group) completed 36 months of treatment.
"Mycophenolate mofetil was significantly superior to azathioprine with respect to the primary end point, the time to treatment failure," and overall rates of treatment failure were 16.4% with mycophenolate, compared with 32.4% with azathioprine, regardless of which type of induction therapy had been used or where patients resided, Dr. Dooley and her colleagues said (N. Engl. J. Med. 2011;365:1886-95).
"Mycophenolate mofetil was significantly superior to azathioprine."
Among subjects who received mycophenolate mofetil maintenance, renal flares developed in 12.9%, rescue therapy was required in 7.8%, and a doubling of the serum creatinine level was reached in 0.9%. Among subjects who received azathioprine maintenance, renal flares developed in nearly twice as many (23.4%), rescue therapy was required in more than twice as many (17.1%), and a doubling of the serum creatinine level was reached in five times as many (4.5%).
Three patients on azathioprine developed ESRD, compared with none of those taking mycophenolate mofetil.
The overall incidence of adverse events was similar between the two groups, and infections were the most common adverse events in both. The rates of serious infection were low in both groups, at 9.6% with mycophenolate mofetil and 11.7% with azathioprine.
The percentage of patients who withdrew from treatment because of adverse effects was higher with azathioprine (39.6%) than with mycophenolate mofetil (25.2%).
"Although our trial included more patients and was substantially longer than many of the controlled trials involving patients with lupus nephritis, potential outcomes that might appear more frequently after 5-20 years [such as cardiovascular complications and ESRD] cannot be determined, since no further follow-up study is planned," they noted.
"The length of time that mycophenolate mofetil needs to be continued is unknown; hence, improved biomarkers of response are needed to distinguish disease remission from remission that occurs while the patient is receiving treatment," they added.
It is important to note that this maintenance study included only patients who responded well to induction therapy. Thus, the results may not apply to those whose disease is more difficult to treat, Dr. Dooley and her associates said.
The ALMS was supported by Vifor Pharma (formerly Aspreva Pharmaceuticals) as part of the Roche-Aspreva rare diseases collaboration, and by Caudex Medical.