title: Safety and efficacy of intensified versus standard dosing regimens of enteric-coated mycophenolate sodium in de novo renal transplant patients.
abstract: BACKGROUND
  Efficacy and safety of an intensified dosing (ID) regimen of enteric-coated mycophenolate sodium (EC-MPS), which achieves higher mycophenolic acid exposure early posttransplantation, were evaluated in comparison with a standard dosing (SD) regimen.
  
  
  METHODS
  In total, 128 de novo kidney transplant recipients treated with basiliximab induction, cyclosporine A, and steroids were randomized (1:1) to receive EC-MPS as SD (1440 mg/day; n=65) or ID (days 0-14: 2880 mg/day; days 15-42: 2160 mg/day; followed by 1440 mg/day; n=63). Efficacy parameters, safety, and tolerability were assessed over a 6-month study period. The primary endpoint was mean time to first occurrence of treatment failure.
  
  
  RESULTS
  Mean time to treatment failure was 130 days (95% confidence interval [CI]: 81-n/a) in the ID group versus 114 days (95% CI: 15-155) in the SD group (P=0.36). Similar percentages (ID 30.2%; SD 36.9%) experienced treatment failure. Biopsy-proven acute rejection occurred in 2 (3.2%) ID versus 11 (16.9%) SD patients (P<0.001). Three (2.3%) deaths (2 SD, 1 ID) and five (3.9%) graft losses (3 SD, 2 ID) occurred. Renal function, incidence of infection, and hematologic disorders were comparable in both study cohorts. Gastrointestinal disorders occurred in 51 (81.0%) ID and 49 (75.4%) SD patients with overall similar tolerability as assessed by the Gastrointestinal Symptom Rating Scale.
  
  
  CONCLUSIONS
  In this exploratory study, the EC-MPS ID regimen reduced the incidence of rejection and showed a comparable safety and tolerability profile to SD. Further examination of this approach in a larger patient cohort is now warranted to confirm these findings.
authors.affiliation: Department of Nephrology, Heidelberg University Hospital, Heidelberg, Germany. claudia.sommerer@med.uni-heidelberg.de
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommerer
authors.forename: Petra
authors.initials: P
authors.lastname: Glander
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Arns
authors.forename: Tofan
authors.initials: T
authors.lastname: Ariatabar
authors.forename: Stefan
authors.initials: S
authors.lastname: Kramer
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Vogel
authors.forename: Maria
authors.initials: M
authors.lastname: Shipkova
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Fischer
authors.forename: Lutz
authors.initials: L
authors.lastname: Liefeldt
authors.forename: Ruth
authors.initials: R
authors.lastname: Hackenberg
authors.forename: Jan
authors.initials: J
authors.lastname: Schmidt
authors.forename: Martin
authors.initials: M
authors.lastname: Zeier
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D013608:Tablets, Enteric-Coated
chemical_list: D007166:Immunosuppressive Agents; D013608:Tablets, Enteric-Coated; D009173:Mycophenolic Acid