12-month safety and efficacy of everolimus with reduced exposure cyclosporine in de novo renal transplant recipients.
The proliferation signal inhibitor everolimus (Certican), has demonstrated efficacy with full-dose cyclosporine (CsA) (Neoral). Two multicenter randomized controlled studies were performed to compare 12-month efficacy and safety of everolimus 1.5 and 3.0 mg/day with reduced-dose CsA. Study 1 enrolled 237 de novo renal allograft recipients, randomizing 222 nonblack patients to either everolimus 1.5 or 3.0 mg/day, with the Neoral) dose guided by C(2) (monitoring of CsA concentration 2 h after dosing). Study 2 had a similar protocol, with basiliximab included, enrolling 256 recipients and randomizing 243 nonblack patients. In Study 1, there was a lower incidence of acute rejection in nonblack patients on 3 mg/day (16.4%) compared with 1.5 mg/day (25.9%), P = 0.08. In Study 2, the inclusion of basiliximab lowered the overall incidence of acute rejection; 14.3% of nonblack patients (3 mg/day) and 13.6% of nonblack patients (1.5 mg/day) had acute rejection by 12 months (P =0.891). Renal function was preserved throughout the study, with no differences observed between groups within studies. Everolimus was well tolerated with no significant differences between doses. Everolimus, in combination with reduced-dose Neoral), demonstrated efficacy and was well tolerated. Basiliximab allows for utilization of lower doses of everolimus with reduced dosing of Neoral).
Tedesco-Silva
Helio
H
Division of Nephrology, Hospital do Rim e Hipertensao, Sao Paolo, Brazil. heliotedesco@hrim.com.br
Vitko
Stefan
S
Pascual
Julio
J
Eris
Josette
J
Magee
John C
JC
Whelchel
John
J
Civati
Giovanni
G
Campbell
Scott
S
Alves-Filho
Gentil
G
Bourbigot
Bernard
B
Garcia
Valter Duro
VD
Leone
John
J
Esmeraldo
Ronaldo
R
Rigotti
Paolo
P
Cambi
Vincenzo
V
Haas
Tomas
T
D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012449:Safety; D018401:Sample Size; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus