title: Improved rejection prophylaxis with an initially intensified dosing regimen of enteric-coated mycophenolate sodium in de novo renal transplant recipients.
abstract: BACKGROUND
  Approximately half of cyclosporine A-treated renal transplant recipients do not reach sufficient mycophenolic acid (MPA) exposure in the first weeks posttransplantation with standard MPA dosing regimens.
  
  
  METHODS
  Here, we present a prospectively planned meta-analysis of data from two 6-month parallel-run studies that evaluated the effect of an initially intensified versus standard dosing regimen of enteric-coated mycophenolate sodium (EC-MPS). Four hundred forty-one de novo renal transplant recipients were randomized (1:1) to intensified (2 weeks 2880 mg/d; subsequently 4 weeks 2160 mg/d; followed by 1440 mg/d) or standard (1440 mg/d) EC-MPS, with concomitant cyclosporine A treatment and steroids with or without anti-IL-2R induction. Primary endpoint was treatment failure (biopsy-proven acute rejection [BPAR], graft loss, or death) at month 6 posttransplantation.
  
  
  RESULTS
  Treatment failure rates were 17.4% in intensified and 22.4% in standard groups (P=0.110). The incidence of BPAR was 13.8% (intensified) vs. 19.3% (standard; P=0.034). A total of 80.5% (intensified) versus 39.0% (standard) of patients achieved 12 hr MPA-area under the curve more than 30 μg·hr/mL as early as day 3 posttransplant. Renal function, gastrointestinal symptom rating scores, and safety profiles were comparable between treatment groups.
  
  
  CONCLUSIONS
  The initially intensified EC-MPS dosing regimen was associated with higher MPA exposure, significantly lower rate of BPAR, and comparable safety. However, the intensified regimen did not affect graft function or survival.
authors.affiliation: Department of Nephrology, Charité Universitätsmedizin Berlin, Berlin, Germany. klemens.budde@charite.de
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
authors.forename: Helio
authors.initials: H
authors.lastname: Tedesco-Silva
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Arns
authors.forename: Ahmed
authors.initials: A
authors.lastname: Shoker
authors.forename: Martin
authors.initials: M
authors.lastname: Zeier
authors.forename: Marian
authors.initials: M
authors.lastname: Klinger
authors.forename: Beatriz
authors.initials: B
authors.lastname: Rosales
authors.forename: Rowan
authors.initials: R
authors.lastname: Walker
authors.forename: Hans
authors.initials: H
authors.lastname: Prestele
authors.forename: Soniya
authors.initials: S
authors.lastname: Vaidya
authors.forename: Dirk
authors.initials: D
authors.lastname: Kuypers
mesh_terms: D006084:Graft Rejection / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016032:Randomized Controlled Trials as Topic; D013608:Tablets, Enteric-Coated
chemical_list: D007166:Immunosuppressive Agents; D013608:Tablets, Enteric-Coated; D009173:Mycophenolic Acid