“MMF is a safer medication for its lower incidence of adverse effects including leucopenia and amenorrhea.”—Anselm Mak, MD
“MMF is comparable with cyclophosphamide in terms of efficacy in inducing renal remissions, prevention of development of end stage renal failure, and survival benefit in the treatment of patients with proliferative lupus glomerulonephritis,” conclude the study authors who were led by Anselm Mak, MD, of the University of Singapore. Moreover, “MMF is a safer medication for its lower incidence of adverse effects including leucopenia and amenorrhea.”MMF, CTX have similar effects on renal remission, risk of death, ESRF
Researchers analyzed 10 randomized controlled trials comprising 847 proliferative lupus glomerulonephritis patients. Overall, MMF was as effective as cyclophosphamide in inducing renal remission (RR 1.052) and the risks of death (RR 0.709) and end stage renal failure (RR 0.453). Moreover, significantly fewer patients receiving MMF developed amenorrhea and leucopenia. The risks of herpes infection and pneumonia were lower among lupus nephritis patients taking MMF, but the risk of diarrhea was higher in this group.
Translating research into practice: patient selection is key for best use MMF in lupus nephritis
An immunosuppressive agent approved to prevent transplant rejection, MMF is not for every patient with proliferative lupus glomerulonephritis, the authors note.
“Treatment selection for proliferative lupus glomerulonephritis should be individualized based on patient-, physician- and disease-related factors,” they write. “Factors such as patients’ gender, age and ethnicity, presence of comorbidity, financial capability, physicians’ experiences and patients’ concerns, especially side effects and fertility issues, are to be considered and discussed with patients in order to provide them with the most appropriate management strategy,“ the authors stress. Non-white and non-Asian patients seemed to respond best to MMF treatment, according to the meta-analysis.
Other risks of MMF may include first-trimester miscarriages and birth defects in the children of women who have taken it, according to the FDA and MMF manufacturer, Roche. The FDA is also investigating MMF’s link to progressive multifocal leukoencephalopathy (PML).
PML risk still under investigation
“As for PML, this problem may be a little more prevalent in lupus than in other chronic diseases, it is usually associated with some kind of immune suppression, but has been seen in the context of many drugs, not just MMF,” stresses Joan T. Merrill, MD, head of the clinical pharmacology research program at the Oklahoma Medical Research Foundation in Oklahoma City, Oklahoma, and medical director of the Lupus Foundation of America. “The mostly spontaneous reporting of this is not of the same quality as an epidemiologic study, so it is hard to say which treatment is more likely to be associated with more PML cases/patient exposure years.”
Other safety issues can be value judgments, Dr. Merrill points out. “For individual people you cannot always predict which treatment is safer for them than another, so definitive global statements about it being "safer" then cyclophosphamide are not terribly useful” she said.
Ellen M. Ginzler, MD, of the division of rheumatology at State University of New York Downstate Medical Center in Brooklyn, New York, agrees with Dr. Merrill’s comments.
That said, “we can expect new information from the maintenance part of the Aspreva Lupus Management Study (ALMS) and the MAINTAIN trial, but that data will not be available for more than a year, maybe 18 months,” she said. This arm of the ALMS trial will assess how well MMF maintains its effect over longer periods, when compared to the current standard treatments. The MAINTAIN trial is comparing azathioprine with MMF for maintenance therapy in lupus nephritis.
References
1. Mak A, Cheak AAC, Tan JYS et al. Mycophenolate mofetil is as efficacious as, but safer than cyclophosphamide in the treatment of proliferative lupus nephritis: a meta-analysis and meta-regression. Rheumatology. 2009; [epub ahead of print June 3, 2009].
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