Mycophenolate mofetil versus azathioprine in kidney transplant recipients on steroid-free, low-dose cyclosporine immunosuppression (ATHENA): A pragmatic randomized trial.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101231360 Publication Model: eCollection Cited Medium: Internet ISSN: 1549-1676 (Electronic) Linking ISSN: 15491277 NLM ISO Abbreviation: PLoS Med Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science, [2004]-
    • Subject Terms:
      Kidney Transplantation*/adverse effects; Azathioprine/*administration & dosage ; Cyclosporine/*administration & dosage ; Graft Rejection/*prevention & control ; Graft Survival/*drug effects ; Immunosuppressive Agents/*administration & dosage ; Mycophenolic Acid/*administration & dosage; Adult ; Aged ; Azathioprine/adverse effects ; Cyclosporine/adverse effects ; Drug Therapy, Combination ; Female ; Graft Rejection/diagnosis ; Graft Rejection/immunology ; Humans ; Immunosuppressive Agents/adverse effects ; Italy ; Male ; Middle Aged ; Mycophenolic Acid/adverse effects ; Prospective Studies ; Time Factors ; Treatment Outcome
    • Abstract:
      Background: We compared protection of mycophenolate mofetil (MMF) and azathioprine (AZA) against acute cellular rejection (ACR) and chronic allograft nephropathy (CAN) in kidney transplant recipients on steroid-free, low-dose cyclosporine (CsA) microemulsion maintenance immunosuppression.
      Methods and Findings: ATHENA, a pragmatic, prospective, multicenter trial conducted by 6 Italian transplant centers, compared the outcomes of 233 consenting recipients of a first deceased donor kidney transplant induced with low-dose thymoglobulin and basiliximab and randomized to MMF (750 mg twice/day, n = 119) or AZA (75 to 125 mg/day, n = 114) added-on maintenance low-dose CsA microemulsion and 1-week steroid. In patients without acute clinical or subclinical rejections, CsA dose was progressively halved. Primary endpoint was biopsy-proven CAN. Analysis was by intention to treat. Participants were included between June 2007 and July 2012 and followed up to August 2016. Between-group donor and recipient characteristics, donor/recipient mismatches, and follow-up CsA blood levels were similar. During a median (interquartile range (IQR)) follow-up of 47.7 (44.2 to 48.9) months, 29 of 87 biopsied patients on MMF (33.3%) versus 31 of 88 on AZA (35.2%) developed CAN (hazard ratio (HR) [95% confidence interval (CI)]: 1.147 (0.691 to 1.904, p = 0.595). Twenty and 21 patients on MMF versus 34 and 14 on AZA had clinical [HR (95% CI): 0.58 (0.34 to 1.02); p = 0.057) or biopsy-proven subclinical [HR (95% CI): 1.49 (0.76 to 2.92); p = 0.249] ACR, respectively. Combined events [HR (95% CI): 0.85 (0.56 to 1.29); p = 0.438], patient and graft survival, delayed graft function (DGF), 3-year glomerular filtration rate (GFR) [53.8 (40.6;65.7) versus 49.8 (36.8;62.5) mL/min/1.73 m2, p = 0.50], and adverse events (AEs) were not significantly different between groups. Chronicity scores other than CAN predict long-term graft outcome. Study limitations include small sample size and unblinded design.
      Conclusions: In this study, we found that in deceased donor kidney transplant recipients on low-dose CsA and no steroids, MMF had no significant benefits over AZA. This finding suggests that AZA, due to its lower costs, could safely replace MMF in combination with minimized immunosuppression.
      Trial Registration: ClinicalTrials.gov NCT00494741; EUDRACT 2006-005604-14.
      Competing Interests: The authors have declared that no competing interests exist.
    • Comments:
      Comment in: Transpl Int. 2021 Nov;34(11):2001-2003. (PMID: 34612545)
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    • Molecular Sequence:
      ClinicalTrials.gov NCT00494741
      EudraCT 2006-005604-14
    • Accession Number:
      0 (Immunosuppressive Agents)
      83HN0GTJ6D (Cyclosporine)
      HU9DX48N0T (Mycophenolic Acid)
      MRK240IY2L (Azathioprine)
    • Publication Date:
      Date Created: 20210624 Date Completed: 20211004 Latest Revision: 20211210
    • Publication Date:
      20240105
    • Accession Number:
      PMC8224852
    • Accession Number:
      10.1371/journal.pmed.1003668
    • Accession Number:
      34166370