title: Everolimus with optimized cyclosporine dosing in renal transplant recipients: 6-month safety and efficacy results of two randomized studies.
abstract: Two prospective, randomized studies evaluated everolimus 1.5 vs. 3 mg/day with steroids and low-exposure cyclosporine (CsA) (C2 monitoring) in de novo renal transplant patients. Everolimus dosing was adjusted to maintain a minimum trough level of 3 ng/mL. Study 1 (A2306; n=237) had no induction therapy; in Study 2 (A2307; n=256) basiliximab was administered (Days 0 and 4). The primary endpoint was renal function at 6 months. CsA C2 target levels, initially 1200 ng/mL in Study 1 and 600 ng/mL in Study 2, were tapered over time post-transplant. Median creatinine levels in Study 1 were 133 and 132 micromol/L at 6 months in the 1.5 and 3 mg/day groups, respectively, and 130 micromol/L in both groups in Study 2. Biopsy-proven acute rejection (BPAR) occurred in 25.0% and 15.2% of patients in the 1.5 and 3 mg/day groups in Study 1, and 13.7% and 15.1% in Study 2. Incidence of BPAR was significantly higher in patients with an everolimus trough <3 ng/mL. There were no significant between-group differences in the composite endpoint of BPAR, graft loss or death, nor any significant between-group differences in adverse events in either study. Concentration-controlled everolimus with low-exposure CsA provided effective protection against rejection with good renal function.
authors.affiliation: Transplant Centre IKEM, Prague, Czech Republic. stefan.vitko@medicon.cz
authors.forename: Stefan
authors.initials: S
authors.lastname: Vitko
authors.forename: Helio
authors.initials: H
authors.lastname: Tedesco
authors.forename: Josette
authors.initials: J
authors.lastname: Eris
authors.forename: Julio
authors.initials: J
authors.lastname: Pascual
authors.forename: John
authors.initials: J
authors.lastname: Whelchel
authors.forename: John C
authors.initials: JC
authors.lastname: Magee
authors.forename: Scott
authors.initials: S
authors.lastname: Campbell
authors.forename: Giovanni
authors.initials: G
authors.lastname: Civati
authors.forename: Bernard
authors.initials: B
authors.lastname: Bourbigot
authors.forename: Gentil
authors.initials: G
authors.lastname: Alves Filho
authors.forename: John
authors.initials: J
authors.lastname: Leone
authors.forename: Valter Duro
authors.initials: VD
authors.lastname: Garcia
authors.forename: Paolo
authors.initials: P
authors.lastname: Rigotti
authors.forename: Ronaldo
authors.initials: R
authors.lastname: Esmeraldo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cambi
authors.forename: Tomas
authors.initials: T
authors.lastname: Haas
authors.forename: Annette
authors.initials: A
authors.lastname: Jappe
authors.forename: Peter
authors.initials: P
authors.lastname: Bernhardt
authors.forename: Johanna
authors.initials: J
authors.lastname: Geissler
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cretin
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000068338:Everolimus; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011897:Random Allocation; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors; D020123:Sirolimus / Q000008:administration & dosage* / Q000031:analogs & derivatives; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus