title: 12-month safety and efficacy of everolimus with reduced exposure cyclosporine in de novo renal transplant recipients.
abstract: 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).
authors.affiliation: Division of Nephrology, Hospital do Rim e Hipertensao, Sao Paolo, Brazil. heliotedesco@hrim.com.br
authors.forename: Helio
authors.initials: H
authors.lastname: Tedesco-Silva
authors.forename: Stefan
authors.initials: S
authors.lastname: Vitko
authors.forename: Julio
authors.initials: J
authors.lastname: Pascual
authors.forename: Josette
authors.initials: J
authors.lastname: Eris
authors.forename: John C
authors.initials: JC
authors.lastname: Magee
authors.forename: John
authors.initials: J
authors.lastname: Whelchel
authors.forename: Giovanni
authors.initials: G
authors.lastname: Civati
authors.forename: Scott
authors.initials: S
authors.lastname: Campbell
authors.forename: Gentil
authors.initials: G
authors.lastname: Alves-Filho
authors.forename: Bernard
authors.initials: B
authors.lastname: Bourbigot
authors.forename: Valter Duro
authors.initials: VD
authors.lastname: Garcia
authors.forename: John
authors.initials: J
authors.lastname: Leone
authors.forename: Ronaldo
authors.initials: R
authors.lastname: Esmeraldo
authors.forename: Paolo
authors.initials: P
authors.lastname: Rigotti
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cambi
authors.forename: Tomas
authors.initials: T
authors.lastname: Haas
mesh_terms: 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
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus