title: Effect of Early Everolimus-Facilitated Reduction of Tacrolimus on Efficacy and Renal Function in De Novo Liver Transplant Recipients: 24-Month Results for the North American Subpopulation.
abstract: BACKGROUND
  A recent randomized phase III study of 719 de novo liver transplant recipients showed that early everolimus plus reduced-dose tacrolimus (EVR + rTAC) led to significantly better kidney function than standard TAC (TAC-C), without compromising efficacy. In that study, patients from North America (n = 211) had increased risk factors for posttransplant renal insufficiency at study start, relative to patients from Europe and rest of world (eg, worse renal function, more diabetes, older age).
  
  
  METHODS
  A post hoc analysis was performed to assess whether these regional disparities affected study outcomes in North American patients.
  
  
  RESULTS
  In this subpopulation, estimated glomerular filtration rates at randomization were higher in TAC-C over EVR + rTAC (76.4 vs 69.3 mL/min per 1.73 m). Mean changes in estimated glomerular filtration rate values (mL/min per 1.73 m) favored EVR + rTAC over TAC-C at months 12 (+3.7 vs -4.5; P = 0.032), 24 (+2.7 vs -6.6; P = 0.042), and 36 (+4.3 vs -8.1; P = 0.059). The composite efficacy endpoint of treated biopsy-proven acute rejection, graft loss, or death was 10.9%, 14.1%, and 14.1% for EVR + rTAC and 13.1%, 17.2%, and 19.3% for TAC-C at months 12, 24, and 36, respectively.
  
  
  CONCLUSIONS
  Although the North American cohort had more comorbidities, results were consistent with the overall population for efficacy and renal function.
authors.affiliation: 1 Division of General Surgery, Department of Surgery, Washington University School of Medicine, Saint Louis, MO.2 Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medical College, New York, NY.3 Division of Transplant Surgery, Department of Surgery, Medical University of South Carolina, Charleston, SC.4 Division of Abdominal Transplant Surgery, Department of Surgery, Duke University Medical Center, Durham, NC.5 Division of Liver Transplant & Hepatobiliary Surgery, Department of Surgery, Rutgers-New Jersey Medical School, Newark, NJ.6 Novartis AG, Basel, Switzerland.7 Novartis Pharmaceuticals Corporation, East Hanover, NJ.8 Transplant Center, Northwell Health, Manhasset, NY.9 Department of Surgery, University of Chicago Medicine Transplant Institute, University of Chicago, Chicago, IL.
authors.forename: William C
authors.initials: WC
authors.lastname: Chapman
authors.forename: Robert S
authors.initials: RS
authors.lastname: Brown
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Chavin
authors.forename: Debra
authors.initials: D
authors.lastname: Sudan
authors.forename: Baburao
authors.initials: B
authors.lastname: Koneru
authors.forename: Guido
authors.initials: G
authors.lastname: Junge
authors.forename: Gaohong
authors.initials: G
authors.lastname: Dong
authors.forename: Dharmesh
authors.initials: D
authors.lastname: Patel
authors.forename: Lewis
authors.initials: L
authors.lastname: Teperman
authors.forename: John J
authors.initials: JJ
authors.lastname: Fung
mesh_terms: D000328:Adult; D001706:Biopsy; D065095:Calcineurin Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D015897:Comorbidity; D004359:Drug Therapy, Combination; D000068338:Everolimus / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006084:Graft Rejection / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D054624:Health Status Disparities; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D016031:Liver Transplantation / Q000009:adverse effects* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009656:North America; D012307:Risk Factors; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; D016559:Tacrolimus