title: Long-term follow-up of a phase III clinical trial comparing tacrolimus extended-release/MMF, tacrolimus/MMF, and cyclosporine/MMF in de novo kidney transplant recipients.
abstract: BACKGROUND
  In a phase III, open-label, comparative, noninferiority study, 638 subjects receiving de novo kidney transplants were randomized to one of three treatment arms: tacrolimus extended-release (Astagraf XL) qd, tacrolimus (Prograf) bid, or cyclosporine (CsA) bid. All subjects received basiliximab induction, mycophenolate mofetil, and corticosteroids. Safety and efficacy follow-up data through 4 years are reported.
  
  
  METHODS
  Evaluations included patient and graft survival, study drug discontinuations, laboratory values including renal function and development of new-onset diabetes after transplantation, concomitant medications, and adverse events.
  
  
  RESULTS
  At study termination, 129 Astagraf XL, 113 Prograf, and 79 CsA patients had continued follow-up. Demographic and baseline characteristics were similar in all arms. Four-year Kaplan-Meier estimates of patient survival in the Astagraf XL, Prograf, and CsA groups were 93.2, 91.2, and 91.7%, respectively, while graft survival was 84.7, 82.7, and 83.9%, respectively. At least one serious adverse event was reported in the majority of patients in each group during the study (65.9% Astagraf XL, 69.8% Prograf, and 65.6% CsA). Renal function was not significantly different between Astagraf XL and Prograf. HgbA1c levels were collected every 6 months; the 4-year Kaplan-Meier estimate for incidence of HgbA1c levels ≥ 6.5% was significantly higher for both tacrolimus formulations compared to CsA; 41.1% (Astagraf XL), 33.6% (Prograf), and 21.3% (CsA).
  
  
  CONCLUSIONS
  In this 4-year follow-up report, patients receiving Astagraf XL and Prograf showed comparable efficacy and safety profiles, with a higher incidence of new-onset diabetes after transplantation but superior renal function compared to patients receiving CsA.
authors: 1 Nephrology Division, Hospital do Rim E Hipertensão, São Paulo, Brazil. 2 Pinnacle Health, Polyclinic Hospital, Harrisburg, PA. 3 Astellas Scientific and Medical Affairs, Inc., Northbrook, IL. 4 Astellas Pharma Global Development, Northbrook, IL. 5 Address correspondence to: M. Roy First, Astellas Pharma Global Development (APGD), 1 Astellas Way, Northbrook, IL 60062.
authors: Hélio Tedesco
authors: HT
authors: Silva
authors: Harold C
authors: HC
authors: Yang
authors: Herwig-Ulf
authors: HU
authors: Meier-Kriesche
authors: Richard
authors: R
authors: Croy
authors: John
authors: J
authors: Holman
authors: William E
authors: WE
authors: Fitzsimmons
authors: M Roy
authors: MR
authors: First
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D003920:Diabetes Mellitus / Q000209:etiology; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007087:Illinois; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012307:Risk Factors; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus