title: Corticosteroid-Sparing and Optimization of Mycophenolic Acid Exposure in Liver Transplant Recipients Receiving Mycophenolate Mofetil and Tacrolimus: A Randomized, Multicenter Study.
abstract: BACKGROUND
  We conducted a randomized multicenter open-label trial in de novo liver transplant recipients to assess the feasibility and potential benefit of a corticosteroid (CS)-free regimen coupled with tacrolimus (Tac) and dose-intensified mycophenolate mofetil (MMF) further adjusted individually.
  
  
  METHODS
  Adult liver transplant recipients were randomized on the day of transplantation to a CS-free regimen with Tac and MMF starting at 3 g/d and dose adjusted from day 5 according to mycophenolic acid (MPA) exposure (arm A) or a regimen with CS maintained up to 6 months, Tac and fixed-dose MMF (2 g/d) (arm B). The primary end point was the proportion of patients who experienced treated biopsy-proven acute rejection (BPAR) during the first year posttransplant.
  
  
  RESULTS
  One hundred eighty-seven patients were randomized, and 174 comprised the per-protocol population (87 in each arm). The primary objective of noninferiority was met: 7 patients in arm A (8%) and 8 in arm B (9%) experienced treated BPAR in the first year. Two patients in arm A (2%) and 5 in arm B (6%) lost their graft, and 12-month patient survival was similar in both arms (90.8% vs 89.8%; P = 0.86). Adverse events were comparable between arms, except for a lower incidence of de novo diabetes (19.8% vs 32.6%, P = 0.049) and a higher incidence of leukopenia less than 2000/mm (28.6% vs 9.8%; P = 0.001) and neutropenia (26.7% vs 7.9%; P < 0.001) in arm A.
  
  
  CONCLUSIONS
  Mycophenolate mofetil at intensified and individually adjusted dose in combination with Tac in de novo liver transplant recipients allows CS discontinuation from day 1 posttransplant with good tolerance and very low rejection incidence.
authors.affiliation: 1 AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France. 2 CHU de Toulouse, Hôpital Purpan, Département de Néphrologie et Transplantation d'Organes, Toulouse, France. 3 CHU l'Archet 2, Service de Chirurgie Digestive, Nice, France. 4 AP-HP, Hôpital Beaujon, Service d'Hépatologie, Clichy, France. 5 Hôpital de la Croix-Rousse, Service d'Hépatologie, Lyon, France. 6 Hôpital A. Michallon, Service d'Hépato-gastroentérologie, La Tronche, France. 7 Hôpital Pellegrin, Pôle d'hépatogastroentérologie, Bordeaux, France. 8 AP-HP, Hôpital Pitié-Salpétrière, Paris, France. 9 Hôpital Trousseau, Service de Chirurgie Digestive et Transplantation Hépatique, Chambray-Lès-Tours, France. 10 CHU Saint Eloi, Service d'HGE et Transplantation, Université de Montpellier, Montpellier, France. 11 AP-HP, Hôpital Henri Mondor, Service d'Hépatologie, Créteil, France. 12 Roche SAS, Boulogne-Billancourt, France. 13 CHU Limoges, UMR 850 INSERM, Univ. Limoges, Limoges, France.
authors.forename: Faouzi
authors.initials: F
authors.lastname: Saliba
authors.forename: Lionel
authors.initials: L
authors.lastname: Rostaing
authors.forename: Jean
authors.initials: J
authors.lastname: Gugenheim
authors.forename: François
authors.initials: F
authors.lastname: Durand
authors.forename: Sylvie
authors.initials: S
authors.lastname: Radenne
authors.forename: Vincent
authors.initials: V
authors.lastname: Leroy
authors.forename: Martine
authors.initials: M
authors.lastname: Neau-Cransac
authors.forename: Yvon
authors.initials: Y
authors.lastname: Calmus
authors.forename: Ephrem
authors.initials: E
authors.lastname: Salamé
authors.forename: Georges-Philippe
authors.initials: GP
authors.lastname: Pageaux
authors.forename: Christophe
authors.initials: C
authors.lastname: Duvoux
authors.forename: Naila
authors.initials: N
authors.lastname: Taguieva
authors.forename: Gilles
authors.initials: G
authors.lastname: Sinnasse-Raymond
authors.forename: Mylène
authors.initials: M
authors.lastname: Sebagh
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.forename: Pierre
authors.initials: P
authors.lastname: Marquet
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000328:Adult; D000368:Aged; D001706:Biopsy; D065095:Calcineurin Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D005260:Female; D005602:France; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016031:Liver Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011446:Prospective Studies; D012307:Risk Factors; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus