BACKGROUND: ADVANCE (NCT01304836) was a phase 4, multicenter, prospectively randomized, open-label, 24-week study comparing the incidence of posttransplantation diabetes mellitus (PTDM) with 2 prolonged-release tacrolimus corticosteroid minimization regimens. METHODS: All patients received prolonged-release tacrolimus, basiliximab, mycophenolate mofetil and 1 bolus of intraoperative corticosteroids (0-1000 mg) as per center policy. Patients in arm 1 received tapered corticosteroids, stopped after day 10, whereas patients in arm 2 received no steroids after the intraoperative bolus. The primary efficacy variable was the diagnosis of PTDM as per American Diabetes Association criteria (2010) at any point up to 24 weeks postkidney transplantation. Secondary efficacy variables included incidence of composite efficacy failure (graft loss, biopsy-proven acute rejection or severe graft dysfunction: estimated glomerular filtration rate (Modification of Diet in Renal Disease-4) <30 mL/min per 1.73 m), acute rejection and graft and patient survival. RESULTS: The full-analysis set included 1081 patients (arm 1: n = 528, arm 2: n = 553). Baseline characteristics and mean tacrolimus trough levels were comparable between arms. Week 24 Kaplan-Meier estimates of PTDM were similar for arm 1 versus arm 2 (17.4% vs 16.6%; P = 0.579). Incidence of composite efficacy failure, graft and patient survival, and mean estimated glomerular filtration rate were also comparable between arms. Biopsy-proven acute rejection and acute rejection were significantly higher in arm 2 versus arm 1 (13.6% vs 8.7%, P = 0.006 and 25.9% vs 18.2%, P = 0.001, respectively). Tolerability profiles were comparable between arms. CONCLUSIONS: A prolonged-release tacrolimus, basiliximab, and mycophenolate mofetil immunosuppressive regimen is efficacious, with a low incidence of PTDM and a manageable tolerability profile over 24 weeks of treatment. A lower incidence of biopsy-proven acute rejection was seen in patients receiving corticosteroids tapered over 10 days plus an intraoperative corticosteroid bolus versus those receiving an intraoperative bolus only.

Department of Nephrology Dialysis and Transplantation Hôpital Lapeyronie University of Montpellier Medical School France 2 Department of Transplantology and Surgery District Hospital Poznan Poland 3 Department of Nephrology Dialysis and Transplantation Hôpital Pasteur CHU de Nice France 4 Department of Nephrology Transplantcenter IKEM Czech Republic 5 Department of Nephrology Transplantation Dialysis Hôpital Pellegrin Université de Bordeaux France 6 Department of Transplantation Surgery Karolinska University Hospital Sweden 7 Surgery and Abdominal Transplantation Division Department of Surgery Cliniques Universitaires Saint Luc Belgium 8 Department of Urology and Kidney Transplantation of the Surgery Clinic Tartu University Hospital Estonia 9 Department of Infectious Diseases Department of Nephrology University Hospital Essen University Duisburg Essen Germany 10 Division of Nephrology Department of Internal Medicine Maastricht University Medical Centre the Netherlands 11 Global Medical Affairs Astellas Pharma Inc Northbrook Illinois 12 Astellas Pharma Europe Ltd Chertsey United Kingdom 13 Department of Nephrology and Renal Transplantation University Hospitals Leuven Belgium

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NCT01304836