A randomized double-blind comparative study of mycophenolate mofetil and azathioprine in combination with cyclosporine and corticosteroids in primary liver transplant recipients

Russell Wiesner, John Rabkin, Goran Klintmalm, Sue McDiarmid, Alan Langnas, Jeffrey Punch, Paul McMaster, Munci Kalayoglu, Gary Levy, Richard Freeman, Henri Bismuth, Peter Neuhaus, Richard Mamelok, Whedy Wang

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Abstract

Acute hepatic allograft rejection occurs in approximately 50% to 60% of the patients undergoing liver transplantation. In this study, we compared the rate of acute rejection in liver transplant recipients randomized in a double-blind comparative study of treatment with mycophenolate mofetil (MMF) or azathioprine (AZA), both in combination with cyclosporine and corticosteroids. Five hundred sixty-five primary liver transplant recipients were randomly assigned to treatment with MMF, 1 g twice daily intravenously followed by 1.5 g twice daily orally (n = 278), or AZA, 1.0 to 2.0 mg/kg/d intravenously followed by oral administration (n = 287), in combination with cyclosporine and corticosteroids. Patients were followed up for at least 1 year, and efficacy analysis was based on intent-to-treat methods. Acute rejection was defined according to the Banff histological criteria. The two study groups were balanced for demographic and clinical baseline characteristics. The incidence of acute rejection or graft loss was 47.7% in the AZA patients and 38.5% in the MMF patients (P < .03). The incidence of biopsyproven and treated rejection censoring for graft loss was 40.0% in the AZA group versus 31.0% in the MMF group (P < .06). Steroid-resistant rejection requiring treatment with either OKT3 or antithymocyte globulin occurred in 8.2% of AZA patients versus 3.8% in MMF patients (P < .02) Patient and graft survival rates at 1 year posttransplantation were 85.4% in the AZA group and 85.3% in the MMF group (P = not significant). MMF was superior to AZA in preventing acute rejection in the first 6 months posttransplantation. MMF and AZA were equivalent in preventing graft loss at 1 year, and the safety profiles between the two immunosuppressive agents were similar.

Original languageEnglish (US)
Pages (from-to)442-450
Number of pages9
JournalLiver Transplantation
Volume7
Issue number5
DOIs
StatePublished - 2001
Externally publishedYes

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Mycophenolic Acid
Azathioprine
Double-Blind Method
Cyclosporine
Adrenal Cortex Hormones
Liver
Graft Rejection
Muromonab-CD3
Antilymphocyte Serum
Transplant Recipients
Incidence
Graft Survival
Immunosuppressive Agents
Liver Transplantation
Allografts
Oral Administration
Therapeutics
Survival Rate
Steroids
Demography

ASJC Scopus subject areas

  • Surgery
  • Transplantation

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A randomized double-blind comparative study of mycophenolate mofetil and azathioprine in combination with cyclosporine and corticosteroids in primary liver transplant recipients. / Wiesner, Russell; Rabkin, John; Klintmalm, Goran; McDiarmid, Sue; Langnas, Alan; Punch, Jeffrey; McMaster, Paul; Kalayoglu, Munci; Levy, Gary; Freeman, Richard; Bismuth, Henri; Neuhaus, Peter; Mamelok, Richard; Wang, Whedy.

In: Liver Transplantation, Vol. 7, No. 5, 2001, p. 442-450.

Research output: Contribution to journalArticle

Wiesner, R, Rabkin, J, Klintmalm, G, McDiarmid, S, Langnas, A, Punch, J, McMaster, P, Kalayoglu, M, Levy, G, Freeman, R, Bismuth, H, Neuhaus, P, Mamelok, R & Wang, W 2001, 'A randomized double-blind comparative study of mycophenolate mofetil and azathioprine in combination with cyclosporine and corticosteroids in primary liver transplant recipients', Liver Transplantation, vol. 7, no. 5, pp. 442-450. https://doi.org/10.1053/jlts.2001.23356
Wiesner, Russell ; Rabkin, John ; Klintmalm, Goran ; McDiarmid, Sue ; Langnas, Alan ; Punch, Jeffrey ; McMaster, Paul ; Kalayoglu, Munci ; Levy, Gary ; Freeman, Richard ; Bismuth, Henri ; Neuhaus, Peter ; Mamelok, Richard ; Wang, Whedy. / A randomized double-blind comparative study of mycophenolate mofetil and azathioprine in combination with cyclosporine and corticosteroids in primary liver transplant recipients. In: Liver Transplantation. 2001 ; Vol. 7, No. 5. pp. 442-450.
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AU - Klintmalm, Goran

AU - McDiarmid, Sue

AU - Langnas, Alan

AU - Punch, Jeffrey

AU - McMaster, Paul

AU - Kalayoglu, Munci

AU - Levy, Gary

AU - Freeman, Richard

AU - Bismuth, Henri

AU - Neuhaus, Peter

AU - Mamelok, Richard

AU - Wang, Whedy

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