ATLANTA – Mycophenolate mofetil was superior to azathioprine for lupus nephritis maintenance therapy in the 36-month maintenance phase of the Aspreva Lupus Management Study.
Patients who had a partial or complete response to corticosteroids and either mycophenolate mofetil (MMF) or intravenous cyclophosphamide during the 24-week induction phase of the international, randomized, controlled ALMS trial were re-randomized to a double-blind comparison of oral MMF or azathioprine (AZA) for maintenance. In 227 patients in the maintenance phase, MMF, compared with AZA, was associated with significantly longer time to treatment failure, which was defined as a composite of renal flare, sustained doubling of serum creatinine, initiation of rescue therapy for lupus nephritis, progression to end-stage renal disease, or death, Dr. Ellen M. Ginzler reported at the annual meeting of the American College of Rheumatology.
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The probability of being event free at 36 months was about 0.8 and 0.6 in the MMF- and AZA-treated patients, respectively, said Dr. Ginzler of the State University of New York-Downtown Medical Center, Brooklyn.
Similarly, the probability of freedom from renal flare – which was the most common component of the primary end point composite – was greater in the MMF-treated patients than in the AZA-treated patients (about 0.85 vs. about 0.75 at 36 months, respectively).
"During the 3-year maintenance follow-up, overall, 16% of MMF-treated and 32% of AZA-treated subjects progressed to the primary end point of treatment failure," Dr. Ginzler said, noting that when assessed by the type of induction treatment received, fewer intravenous cyclophosphamide induction subjects than MMF induction subjects were treatment failures in the maintenance phase, but MMF (for maintenance) remained superior to AZA for both induction subsets.
Similarly, failure rates were consistently in favor of MMF for all races (although only statistically significantly for blacks), and for all geographic regions evaluated, she noted.
MMF also was superior to AZA on all secondary end points (end-stage renal disease, renal flare, doubling of creatinine, and need for rescue meds), as well as on a secondary efficacy end point that used a broader definition of time to treatment failure: a composite of development of major extra-renal flares, a need for rescue therapy not permitted in the study protocol for extrarenal flares, and withdrawal from the study for any reason.
"Although not statistically significantly different among the two treatment groups, MMF-treated subjects had a better outcome based on all efficacy end points," Dr. Ginzler said.
She also noted that historically, at the conclusion of induction therapy for lupus nephritis, the percentage of patients who achieve complete remission is disappointing. Often, however, patients with a partial response continue to improve during maintenance therapy.
"This is clearly the case overall in the ALMS trial, which demonstrates no difference between MMF and AZA in rate of development of complete renal remission," she said.
MMF in the maintenance phase was given at a target dose of 1 g twice daily, and AZA was given at a target dose of 2 mg/kg per day. Dose adjustments were allowed (up to 3 g twice daily and 3 mg/kg per day for MMF and AZA, respectively) and prednisone was allowed at a maximum dose of 10 mg/day or equivalent.
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