Three-year efficacy and safety results from a study of everolimus versus mycophenolate mofetil in de novo renal transplant patients.
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.
Vítko
Stefan
S
Institute of Clinical and Experimental Medicine, Praha, Czech Republic.
Margreiter
Raimund
R
Weimar
Willem
W
Dantal
Jacques
J
Kuypers
Dirk
D
Winkler
Michael
M
Øyen
Ole
O
Viljoen
Hendrik G
HG
Filiptsev
Pavel
P
Sadek
Sami
S
Li
Yulan
Y
Cretin
Nathalie
N
Budde
Klemens
K
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
D000305:Adrenal Cortex Hormones; D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D003404:Creatinine; D009173:Mycophenolic Acid; D020123:Sirolimus