Mycophenolate mofetil for the treatment of a first acute renal allograft rejection: three-year follow-up. The Mycophenolate Mofetil Acute Renal Rejection Study Group.

BACKGROUND: Mycophenolate mofetil (MMF) has previously been shown to be significantly better than azathioprine (AZA) in the treatment of first acute renal transplant (Tx) rejection by 6 months after initiation of treatment. This report analyzes the 3-year safety and efficacy data from this cohort of patients.

METHODS: Renal Tx recipients with a first rejection episode occurring within 6 months after a first or second cadaver or living donor Tx were randomized, double-blind, to receive MMF (1.5 g b.i.d., n=113) or AZA (1-2 mg/kg, n = 108); both treatment arms also received i.v. corticosteroids (5 mg/kg/day for 5 days) followed by a steroid taper in conjunction with cyclosporine. Patients remained on blinded study medication for 1 year, after which they were converted to open-label study medication at the same dosage. All patients, including those who terminated early (<3 yr) were followed for patient and graft survival, chronic renal allograft dysfunction (CRAD), and malignancy. CRAD was determined by the presence of at least two of the following: a biopsy with chronic rejection, proteinuria >750 mg/day, or an increase in serum creatinine >1 mg/dl over baseline. Patients who continued to receive the assigned medication were followed for additional rejections, renal function, and adverse events including infections.

RESULTS: A total of 67 (59.3%) MMF-treated and 56 (51.9%) AZA-treated patients completed the 3-year study; follow-up was available for all randomized patients except one. At 3 years, the cumulative incidence of first subsequent biopsy-proven or presumptive rejection while receiving study drug was 42.2% in the MMF-treated and 68.8% in the AZA-treated patients; a difference of 26.6% (95% confidence interval: 13.4-39.9%). At 3 years, 19.6% of all MMF-treated and 24.1% of all AZA-treated patients lost their Tx or had died. Renal function was similar in both groups. The combined end point of CRAD or Tx loss without CRAD occurred in 23% and 26% of all MMF- and all AZA-treated patients, respectively. Leukopenia, diarrhea, and abdominal pain were the most commonly associated adverse events of MMF treatment. Malignancies (predominantly cutaneous) occurred in 14.2% of MMF-treated patients and 10.2% of AZA-treated patients. Three lymphomas occurred in each treatment arm.

CONCLUSION: The addition of MMF at the time of renal Tx rejection reduces the frequency of subsequent rejections without causing new limiting side effects. Although Tx survival was better in the MMF group, comparison with AZA was confounded by the rate of premature terminations in both treatment groups.