Mycophenolate mofetil (CellCept) shows promise in treating lupus.
New research shows promising results in the use of mycophenolate mofetil (CellCept) to treat lupus — without severe side effects associated with the current standard of care.
Mycophenolate mofetil (MMF) is an immunosuppressive drug used primarily to prevent the body from rejecting a transplanted organ. Anecdotal series and small, prospective, controlled trials have suggested that MMF may be effective in induction therapy for patients suffering from lupus nephritis, the researchers say, and they wanted to conduct a larger trial. Their results were published in the Nov. 24, 2005, issue of the New England Journal of Medicine.
Until now, intravenous cyclophosphamide (IVC) has been the standard of care for treating lupus. The side effects of IVC therapy include nausea, vomiting, hair loss, and infertility. Some of the side effects have been so severe that patients decide not to undergo treatment.
In this trial, researchers conducted a 24-week randomized, open-label, noninferiority trial comparing oral MMF (giving an initial dose of 1,000 mg/day and increasing to 3,000 mg/day) with monthly IVC (giving 0.5 g/m2 of body-surface area and increasing to 1.0 g/m2) as induction therapy for active lupus nephritis. Of 140 patients recruited, 71 were randomly assigned to receive MMF and 69 were randomly assigned to receive IVC. Patients who did not have an early response were allowed a change to the alternative regimen at 12 weeks.
At 12 weeks, 56 patients receiving MMF and 42 receiving IVC had satisfactory early responses. In the intention-to-treat analysis, 16 of the 71 patients (22.5%) receiving MMF and four of the 69 patients receiving IVC (5.8%) had complete remission, for an absolute difference of 16.7 percentage points. Partial remission occurred in 21 of the 71 patients (29.6%) and 17 of the 69 patients (24.6%), respectively.
A total of 24 patients were withdrawn from the study; nine in the MMF group and 15 in the IVC group. Two patients died in the IVC group during treatment. One patient died from a cerebral hemorrhage within a week of receiving the first dose. The other patient received two doses, the second of which was delayed by sepsis. The patient died three weeks later; the death was related to active lupus and recurrent sepsis. A third patient assigned to IVC declined therapy and died from pulmonary hemorrhage and renal failure at another hospital. No patients in the MMF group died.
Infection and gastrointestinal side effects accounted for most of the adverse events. Severe infections such as pneumonia and lung abscess, necrotizing fasciitis, and gram-negative sepsis occurred only with IVC. Pyogenic infections were significantly less frequent among patients receiving MMF than among those receiving IVC.
Hospitalizations for vomiting and dehydration also occurred in five patients (a total of seven episodes) receiving IVC. Diarrhea occurred more frequently with MMF (15 patients) than with IVC (two patients).
In summary, induction therapy with MMF was superior to IVC in inducing complete remission of lupus nephritis in this study and appeared to be better tolerated, the researchers say. Unresolved issues, however, include determining the flare rate after induction with MMF, as compared with that for IVC, and determining the appropriate dose and duration of MMF maintenance therapy.
In an accompanying editorial, a physician discusses which type of lupus patient may best benefit from MMF treatment. MMF remains inadequately tested in patients with rapidly progressive nephritis and acute renal failure, says W. Joseph McCune, MD, professor in the division of rheumatology, department of internal medicine, at the University of Michigan Medical Center in Ann Arbor. "At this time, the sickest patients arguably should be treated with boluses of cyclophosphamide and corticosteroids."
Patients with new, mild-to-moderately-severe nephritis and intact renal function, for whom fertility is a paramount concern, however, can reasonably start treatment with MMF, he says. For patients who occupy the middle ground, long-term studies will need to guide treatment choices.
"It is highly likely that individual patients may respond unpredictably to one treatment or the other, and it may be necessary to change the treatment when the clinical response is inadequate," McCune says. "The favorable response to mycophenolate mofetil, as compared with monthly intravenous cyclophosphamide, strongly suggests that, after disease control is achieved, mycophenolate mofetil will, in most patients, prove to be superior to quarterly intravenous cyclophosphamide as a long-term treatment.
"Lupus nephritis appears to respond better to immunosuppressive therapy when treatment is instituted early in the course of disease," he continues. "I predict that wider use of mycophenolate mofetil, with its favorable side effect profile, will be associated with earlier treatment of less advanced disease and with more favorable outcomes."
New research shows promising results in the use of mycophenolate mofetil (CellCept) to treat lupus without severe side effects associated with the current standard of care.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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