title: Individualized mycophenolate mofetil dosing based on drug exposure significantly improves patient outcomes after renal transplantation.
abstract: Efficacy and safety of mycophenolate mofetil (MMF) may be optimized with individualized doses based on therapeutic monitoring of its active metabolite, mycophenolic acid (MPA). In this 12-month study, 137 renal allograft recipients from 11 French centers receiving basiliximab, cyclosporine A, MMF and corticosteroids were randomized to receive either concentration-controlled doses or fixed-dose MMF. A novel Bayesian estimator of MPA AUC based on three-point sampling was used to individualize doses on posttransplant days 7 and 14 and months 1, 3 and 6. The primary endpoint was treatment failure (death, graft loss, acute rejection and MMF discontinuation). Data from 65 patients/group were analyzed. At month 12, the concentration-controlled group had fewer treatment failures (p = 0.03) and acute rejection episodes (p = 0.01) with no differences in adverse event frequency. The MMF dose was higher in the concentration-controlled group at day 14 (p < 0.0001), month 1 (p < 0.0001) and month 3 (p < 0.01), as were median AUCs on day 14 (33.7 vs. 27.1 mg*h/L; p = 0.0001) and at month 1 (45.0 vs. 30.9 mg*h/L; p < 0.0001). Therapeutic MPA monitoring using a limited sampling strategy can reduce the risk of treatment failure and acute rejection in renal allograft recipients 12 months posttransplant with no increase in adverse events.
authors.affiliation: Department of Nephrology, University Hospital, Limoges, France. yannick.lemeur@chu-brest.fr
authors.forename: Y
authors.initials: Y
authors.lastname: Le Meur
authors.forename: M
authors.initials: M
authors.lastname: Büchler
authors.forename: A
authors.initials: A
authors.lastname: Thierry
authors.forename: S
authors.initials: S
authors.lastname: Caillard
authors.forename: F
authors.initials: F
authors.lastname: Villemain
authors.forename: S
authors.initials: S
authors.lastname: Lavaud
authors.forename: I
authors.initials: I
authors.lastname: Etienne
authors.forename: P-F
authors.initials: PF
authors.lastname: Westeel
authors.forename: B
authors.initials: B
authors.lastname: Hurault de Ligny
authors.forename: L
authors.initials: L
authors.lastname: Rostaing
authors.forename: E
authors.initials: E
authors.lastname: Thervet
authors.forename: J C
authors.initials: JC
authors.lastname: Szelag
authors.forename: J-P
authors.initials: JP
authors.lastname: Rérolle
authors.forename: A
authors.initials: A
authors.lastname: Rousseau
authors.forename: G
authors.initials: G
authors.lastname: Touchard
authors.forename: P
authors.initials: P
authors.lastname: Marquet
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D019540:Area Under Curve; D000077552:Basiliximab; D016572:Cyclosporine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012449:Safety; D014184:Transplantation, Homologous
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D016572:Cyclosporine; D000077552:Basiliximab; D009173:Mycophenolic Acid