Everolimus (Certican) 12-month safety and efficacy versus mycophenolate mofetil in de novo renal transplant recipients.
BACKGROUND
Everolimus is a proliferation inhibitor designed to target chronic rejection, including prevention of acute rejection. Everolimus blocks growth factor-mediated transduction signals, preventing organ rejection by a mechanism different than that of calcineurin inhibitors and of mycophenolate mofetil (MMF). METHODS.: Everolimus (1.5 mg or 3 mg daily) was compared with MMF (2 g daily) in a randomized, multicenter, multinational, 12-month double-blind, double-dummy and 2-year open-label, phase 3 trial in de novo renal allograft recipients (n = 588) who also received cyclosporine and corticosteroids as part of a triple immunosuppressive regimen.


RESULTS
At 12 months, there were no statistically significant differences between doses of 1.5 and 3 mg/day everolimus and MMF (2 g/day) in incidence of biopsy-proven acute rejection (23.2%, 19.7%, and 24.0%, respectively), graft loss (4.6%, 10.6%, and 9.2%), or death (5.2%, 4.0%, and 2.6%), respectively. Everolimus 1.5 mg/day and MMF were generally equally well tolerated. Both were better tolerated than everolimus 3 mg/day. The incidence of cytomegalovirus infection was significantly lower in patients receiving either 1.5 or 3 mg/day everolimus than in those receiving MMF (5.2% and 7.6% vs. 19.4%, respectively) (P = .001).


CONCLUSIONS
Everolimus is effective in preventing acute rejection and graft loss in de novo renal allograft recipients receiving a triple immunosuppressive regimen. Prevention of acute rejection, along with reduction in cytomegalovirus infection, addresses two factors known to contribute to chronic rejection in such patients.
Vítko
Stefan
S
Transplant Center, IKEM, Transplant Center, Videnská Street 1958/9, 140 21 Prague 4, Czech Republic.
Margreiter
Raimund
R
Weimar
Willem
W
Dantal
Jacques
J
Viljoen
Hendrik G
HG
Li
Yulan
Y
Jappe
Annette
A
Cretin
Nathalie
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D000068338:Everolimus; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D012449:Safety; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D000068338:Everolimus; D009173:Mycophenolic Acid; D020123:Sirolimus; D008775:Methylprednisolone