title: Two corticosteroid-free regimens-tacrolimus monotherapy after basiliximab administration and tacrolimus/mycophenolate mofetil-in comparison with a standard triple regimen in renal transplantation: results of the Atlas study.
abstract: BACKGROUND
  The side effects associated with corticosteroids have led to efforts to minimize their use in renal transplant patients. In this study we compared two corticosteroid-free tacrolimus-based regimens with a standard triple therapy.
  
  
  METHODS
  This was a 6-month, phase III, open-label, parallel-group, multicenter study. The total analysis set comprised 451 patients, randomized (1:1:1) to receive tacrolimus (Tac) monotherapy following basiliximab (Bas) administration (n=153), Tac/mycophenolate mofetil (MMF) (n=151), or, Tac/MMF/corticosteroids triple therapy as a control (n=147).
  
  
  RESULTS
  The study was completed by 91.2% (triple therapy), 94.7% (Tac/MMF), and 82.4% (Bas/Tac) of patients. Patient baseline characteristics were similar in all groups. The incidences of biopsy-proven acute rejection were 8.2% (triple therapy), 30.5% (Tac/MMF), and 26.1% (Bas/Tac), p<0.001 (multiple test for comparison with triple therapy); Bas/Tac vs. Tac/MMF, p=ns. The incidences of corticosteroid-resistant acute rejection were 2.0%, 4.0%, and 5.2%, p=ns. Graft survival (95.9%, 96.7%, and 94.7%, p=ns) and patient survival (100%, 99.3%, and 99.3%, p=ns) were similar in all groups. Median serum creatinine at month 6 was 123.0 micromol/L (triple therapy), 134.7 micromol/L (Tac/MMF) and 135.8 micromol/L (Bas/Tac). The overall safety profiles were similar; differences (p<0.05) were reported for anaemia (24.5% vs. 12.6% vs. 14.5%), diarrhoea (12.9% vs. 17.9% vs. 5.9%), and leukopenia (7.5% vs. 18.5% vs. 5.9%) for the triple therapy, Tac/MMF, and Bas/Tac group, respectively. The incidences of new-onset diabetes mellitus were 4.6%, 7.1%, and 1.4%, respectively.
  
  
  CONCLUSIONS
  Corticosteroid-free immunosuppression was feasible with the Bas/Tac and the Tac/MMF regimens. Both corticosteroid-free regimens were equally effective in preventing acute rejection, with the Bas/Tac therapy offering some safety benefits.
authors.affiliation: Department of Nephrology, IKEM, Prague, Czech Republic and Department of Nephrology, Wroclaw Medical University, Wroclaw, Poland. stvi@medicon.cz
authors.forename: Stefan
authors.initials: S
authors.lastname: Vítko
authors.forename: Marian
authors.initials: M
authors.lastname: Klinger
authors.forename: Kaija
authors.initials: K
authors.lastname: Salmela
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Wlodarczyk
authors.forename: Gunnar
authors.initials: G
authors.lastname: Tydèn
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Senatorski
authors.forename: Marek
authors.initials: M
authors.lastname: Ostrowski
authors.forename: Per
authors.initials: P
authors.lastname: Fauchald
authors.forename: Franciszek
authors.initials: F
authors.lastname: Kokot
authors.forename: Sergio
authors.initials: S
authors.lastname: Stefoni
authors.forename: Ferenc
authors.initials: F
authors.lastname: Perner
authors.forename: Kerstin
authors.initials: K
authors.lastname: Claesson
authors.forename: Marco
authors.initials: M
authors.lastname: Castagneto
authors.forename: Uwe
authors.initials: U
authors.lastname: Heemann
authors.forename: Mario
authors.initials: M
authors.lastname: Carmellini
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Squifflet
authors.forename: Markus
authors.initials: M
authors.lastname: Weber
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Segoloni
authors.forename: Lars
authors.initials: L
authors.lastname: Bäckman
authors.forename: Heide
authors.initials: H
authors.lastname: Sperschneider
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Krämer
mesh_terms: D000305:Adrenal Cortex Hormones; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000077552:Basiliximab; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D016019:Survival Analysis; D016559:Tacrolimus / Q000008:administration & dosage* / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab; D009173:Mycophenolic Acid; D016559:Tacrolimus