title: Three-year efficacy and safety results from a study of everolimus versus mycophenolate mofetil in de novo renal transplant patients.
abstract: Everolimus 1.5 or 3 mg/day was compared with mycophenolate mofetil (MMF) 2 g/day in a randomized, multicenter 36-month trial in de novo renal allograft recipients (n = 588) receiving cyclosporine microemulsion (CsA) and corticosteroids. The study was double-blind until all patients had completed 12 months, then open-label. By 36 months, graft loss occurred in 7.2, 16.7 and 10.7% of patients in the everolimus 1.5, 3 mg/day, and MMF groups, respectively (p = 0.0048 for everolimus 1.5 mg/day vs. 3 mg/day); efficacy failure (biopsy-proven acute rejection (BPAR), graft loss, death or lost to follow-up) occurred in 33.0, 38.9 and 37.2% of patients (p = 0.455 overall), respectively. Mortality and incidence of BPAR were comparable in all groups. Creatinine values were higher in everolimus groups, requiring a protocol amendment that recommended lower CsA exposure. Diarrhea, lymphocele, peripheral edema and hyperlipidemia were more common among everolimus-treated patients, whereas viral infections, particularly cytomegalovirus infection, increased in the MMF group. Overall safety and tolerability were better with MMF and everolimus 1.5 mg/day than with everolimus 3 mg/day. In conclusion, at 36 months, an immunosuppressive regimen containing everolimus 1.5 mg/day had equivalent patient, and graft survival and rejection rates compared with MMF in de novo renal transplant recipients, whereas everolimus 3 mg/day had inferior graft survival. Renal dysfunction in everolimus cohorts necessitates close monitoring.
authors.affiliation: Institute of Clinical and Experimental Medicine, Praha, Czech Republic.
authors.forename: Stefan
authors.initials: S
authors.lastname: Vítko
authors.forename: Raimund
authors.initials: R
authors.lastname: Margreiter
authors.forename: Willem
authors.initials: W
authors.lastname: Weimar
authors.forename: Jacques
authors.initials: J
authors.lastname: Dantal
authors.forename: Dirk
authors.initials: D
authors.lastname: Kuypers
authors.forename: Michael
authors.initials: M
authors.lastname: Winkler
authors.forename: Ole
authors.initials: O
authors.lastname: Øyen
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Viljoen
authors.forename: Pavel
authors.initials: P
authors.lastname: Filiptsev
authors.forename: Sami
authors.initials: S
authors.lastname: Sadek
authors.forename: Yulan
authors.initials: Y
authors.lastname: Li
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cretin
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001706:Biopsy; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use; D004311:Double-Blind Method; D004655:Emulsions / Q000627:therapeutic use; D000068338:Everolimus; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D003404:Creatinine; D009173:Mycophenolic Acid; D020123:Sirolimus