title: Incidence of Posttransplantation Diabetes Mellitus in De Novo Kidney Transplant Recipients Receiving Prolonged-Release Tacrolimus-Based Immunosuppression With 2 Different Corticosteroid Minimization Strategies: ADVANCE, A Randomized Controlled Trial.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 1 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.
authors.forename: Georges
authors.initials: G
authors.lastname: Mourad
authors.forename: Maciej
authors.initials: M
authors.lastname: Glyda
authors.forename: Laetitia
authors.initials: L
authors.lastname: Albano
authors.forename: Ondrej
authors.initials: O
authors.lastname: Viklický
authors.forename: Pierre
authors.initials: P
authors.lastname: Merville
authors.forename: Gunnar
authors.initials: G
authors.lastname: Tydén
authors.forename: Michel
authors.initials: M
authors.lastname: Mourad
authors.forename: Aleksander
authors.initials: A
authors.lastname: Lõhmus
authors.forename: Oliver
authors.initials: O
authors.lastname: Witzke
authors.forename: Maarten H L
authors.initials: MHL
authors.lastname: Christiaans
authors.forename: Malcolm W
authors.initials: MW
authors.lastname: Brown
authors.forename: Nasrullah
authors.initials: N
authors.lastname: Undre
authors.forename: Gbenga
authors.initials: G
authors.lastname: Kazeem
authors.forename: Dirk R J
authors.initials: DRJ
authors.lastname: Kuypers
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D003692:Delayed-Action Preparations; D003920:Diabetes Mellitus / Q000453:epidemiology* / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage*; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D015994:Incidence; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage*; D015995:Prevalence; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus