title: Comparison of sirolimus with azathioprine in a tacrolimus-based immunosuppressive regimen in lung transplantation.
abstract: BACKGROUND
  Lung transplantation has evolved into a life-saving therapy for select patients with end-stage lung diseases. However, long-term survival remains limited because of chronic rejection. Sirolimus is beneficial in preventing cardiac rejection and may decrease rejection after lung transplantation.
  
  
  OBJECTIVE
  To determine the potential benefit versus risk of sirolimus in lung transplantation.
  
  
  METHODS
  We conducted a multicenter randomized, open label controlled trial comparing sirolimus (SIR) with azathioprine (AZA) in a tacrolimus-based immunosuppressive regimen in lung transplantation. The primary end point was the incidence of acute rejection at 1 year after transplantation between the two study groups.
  
  
  RESULTS
  One hundred eighty-one patients were randomized to be included in this study. At 1 year after transplantation, there was no significant difference in the incidence of grade A acute rejection between the two study groups. Similarly, the incidence of chronic rejection and graft survival was no different between the two study groups. Cytomegalovirus infection was decreased in the SIR arm compared with the AZA arm (relative risk, 0.67 [95% confidence interval, 0.55, 0.82]; P < 0.01). There was a higher rate of adverse events leading to early discontinuation of SIR (64%) compared with AZA (49%) during the course of this study.
  
  
  CONCLUSIONS
  Sirolimus, an mTOR inhibitor, did not decrease the incidence of acute rejection at 1 year compared with azathioprine in lung transplantation. These results differ from previous results in cardiac and renal transplantation and emphasize the need for multicenter randomized controlled trials in lung transplantation. Clinical trial registered with www.clinicaltrials.gov (NCT 00321906).
authors.affiliation: University of Chicago Medical Center, Chicago, Illinois, USA. sbhorade@medicine.bsd.uchicago.edu
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Bhorade
authors.forename: Vivek N
authors.initials: VN
authors.lastname: Ahya
authors.forename: Maher A
authors.initials: MA
authors.lastname: Baz
authors.forename: Vincent G
authors.initials: VG
authors.lastname: Valentine
authors.forename: Selim M
authors.initials: SM
authors.lastname: Arcasoy
authors.forename: Robert B
authors.initials: RB
authors.lastname: Love
authors.forename: Harish
authors.initials: H
authors.lastname: Seethamraju
authors.forename: Charles G
authors.initials: CG
authors.lastname: Alex
authors.forename: Remzi
authors.initials: R
authors.lastname: Bag
authors.forename: Nilto C
authors.initials: NC
authors.lastname: Deoliveira
authors.forename: Aliya
authors.initials: A
authors.lastname: Husain
authors.forename: Wickii T
authors.initials: WT
authors.lastname: Vigneswaran
authors.forename: Jeff
authors.initials: J
authors.lastname: Charbeneau
authors.forename: Jerry A
authors.initials: JA
authors.lastname: Krishnan
authors.forename: Ramon
authors.initials: R
authors.lastname: Durazo-Arvizu
authors.forename: Lourdes
authors.initials: L
authors.lastname: Norwick
authors.forename: Edward
authors.initials: E
authors.lastname: Garrity
mesh_terms: D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use*; D001989:Bronchiolitis Obliterans / Q000209:etiology; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000188:drug therapy / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D001379:Azathioprine; D020123:Sirolimus; D016559:Tacrolimus