A blinded, long-term, randomized multicenter study of mycophenolate mofetil in cadaveric renal transplantation results at three years

Timothy H. Mathew, P. Keown, I. Hardie, H. Isoniemi, P. Morris, P. Belitsky, B. Buchholz, R. Walker, G. Kirste, C. Stiller, D. Tiller, P. Halloran, P. Daloze, D. Russel, P. Vialtel, U. Binswanger, J. A C Buckels, J. L. Touraine, D. Hickey, G. RemuzziF. T. Lam, M. Navarro, E. Ramos, M. Rees

Research output: Contribution to journalArticle

Abstract

Background. Three large-scale clinical trials conducted in North America, Europe, and Australia showed that mycophenolate mofetil (MMF) decreases the incidence of acute renal allograft rejection in the first 6 months after transplant compared with placebo or azathioprine. This study extends the randomized, prospective, double-blind trial of MMF conducted by the Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group. Methods. Patients (n=503) were randomized to receive 100-150 mg of azathioprine (AZA) (n=166), 2 g of MMF (n=173), or 3 g of MMF (n=164) per day, in conjunction with cyclosporine and prednisone from the time of transplantation. Results. During the first 6 months, the incidence of biopsy- proven acute graft rejection (BPR) was reduced by ~50% in the MMF 2 g (19.7%) and MMF 3 g (15.9%) groups compared with the AZA group (35.5%). The incidence of treatment failure during the first 6 months, including BPR, death, graft loss, and early withdrawal without prior BPR, was significantly decreased: ZA, 50%, compared with MMF 2 g, 38.2% (P=0.0287), and MMF 3 g, 34.8% (P=0.0045). At 3 years after transplant, both intent-to-treat and on- study (censoring at 90 days after treatment) analyses of graft and patient survival showed a trend toward advantage for MMF 2 g and 3 g vs. AZA (intent- to-treat: 81.9% and 84.8% vs. 80.2%; on-study: 84.0% and 86.4% vs. 82.7%), although this trend did not reach statistical significance. Rejection was the principal cause of graft loss in all groups: AZA, 9.9%; MMF 2 g, 5.8%; and MMF 3 g, 3.0%. Graft function (intent-to-treat and on-study) was comparable in all three groups at 3 years. Gastrointestinal toxicity, leukopenia, and tissue-invasive cytomegalovirus disease were more common in the MMF 3 g group both during and after the first posttransplant year. Lymphoproliferative disorders were diagnosed in one AZA (0.6%), two MMF 2 g (1.2%), and three MMF 3 g (1.8%) patients. Other (non-lymphoproliferative disorders, noncutaneous) malignancies occurred in six AZA (3.7%), four MMF 2 g (2.3%), and nine MMF 3 g (5.5%) patients. Mortality was comparable in all three groups (ZA, 8.6%; MMF 2 g, 4.7%; MMF 3 g, 9.1%) by 3 years of follow-up. Conclusion. MMF significantly reduced the incidence of rejection in the first 6 months, but there was not a significant improvement in graft survival throughout the 3 years after cadaver kidney transplantation.

Original languageEnglish
Pages (from-to)1450-1454
Number of pages5
JournalTransplantation
Volume65
Issue number11
DOIs
Publication statusPublished - Jun 15 1998

    Fingerprint

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Mathew, T. H., Keown, P., Hardie, I., Isoniemi, H., Morris, P., Belitsky, P., Buchholz, B., Walker, R., Kirste, G., Stiller, C., Tiller, D., Halloran, P., Daloze, P., Russel, D., Vialtel, P., Binswanger, U., Buckels, J. A. C., Touraine, J. L., Hickey, D., ... Rees, M. (1998). A blinded, long-term, randomized multicenter study of mycophenolate mofetil in cadaveric renal transplantation results at three years. Transplantation, 65(11), 1450-1454. https://doi.org/10.1097/00007890-199806150-00007