Source: DGNews  |  Posted 8 years ago

By Roberta Friedman, PhD

SAN DIEGO, CA -- November 18, 2003 -- Mycophenolate mofetil (MMF) is as effective as cyclophosphamide for induction therapy in patients with severe lupus nephritis, according to a multicentre trial carried out across the United States.

Interim 6-month findings of the head to head comparison in 140 patients with active lupus nephritis were presented here November 15th at the 36th Annual Meeting of the American Society of Nephrology.

"MMF was superior in this population at inducing remission," said Gerald Appel, MD, professor of clinical medicine and director, division of nephrology, Columbia Presbyterian Medical Center, New York. He cautioned, however, that while MMF appears to show potential as an alternative to cyclophosphamide, "It is only 6 months [of] follow up" data that so far are available for the trial."

The study randomised 71 patients to treatment with MMF dosed at 1 g a day and then increased to 3 g daily, a much higher dose than is used to treat other conditions, Dr. Appel noted. Yet, surprisingly, patients tolerated it, he said. "The dose tolerated was much higher than I would have expected," he added.

For the 69 patients assigned to cyclophosphamide, the intravenous dose was 0.5 g/m2 monthly with increases to 0.75 g/m2 and 1 g/m2 if white cell counts permitted. After 12 weeks, study subjects could cross over if they did not improve by 30% over entry values for at least one index of renal function.

Patients had World Health Organisation class III to V lupus nephritis at study entry, meaning that they had focal glomerulonephritis (approximately 15% of biopsies), diffuse glomerulonephritis (about 25% of biopsies), or diffuse membranous glomerulonephritis (about 8% of biopsies). All patients were treated with steroids.

The primary outcome was return of creatinine, proteinuria, or urine sediment to normal -- a goal that is "very difficult to achieve," commented Dr. Appel. Given the goal, he said, the study was "probably mis-designed." Study investigators documented complete remission for 22.5% of 71 patients taking MMF and 5.8% of 69 on cyclophosphamide (P <.005). Partial remissions, defined as more than 50% improvement in abnormal renal measures, with none worsening, did not differ between the treatments.

African American subjects, for whom the prognosis is known to be poor, had fewer instances of complete remission on MMF compared to participants of other racial backgrounds, Dr. Appel said. But no African American had complete remission on cyclophosphamide in the trial. Two thirds of the African Americans in the study tolerated the full 3-g dose, he added.

MMF treatment led to more frequent gastrointestinal adverse effects than did cyclophosphamide -- 14 patients versus two. All three deaths in the study occurred in the cyclophosphamide group. Less hair loss or menstrual irregularities occurred with MMF.

While infection rates were similar for the two treatments, only cyclophosphamide was associated with pneumonia, sepsis and lung abscess (one instance each).

Based on findings of another presentation at the meeting (Abstract SA-FC173), said Dr. Appel, the best strategy for lupus nephritis might be to induce with cyclophosphamide and switch to MMF.

[Study title: Multicenter Controlled Trial of Mycophenolate Mofetil (MMF) vs. Intravenous Cyclophosphamide (IVC) as Induction Therapy for Severe Lupus Nephritis (LN). Abstract SA-FC171]