Everolimus with optimized cyclosporine dosing in renal transplant recipients: 6-month safety and efficacy results of two randomized studies.
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.
Vitko
Stefan
S
Transplant Centre IKEM, Prague, Czech Republic. stefan.vitko@medicon.cz
Tedesco
Helio
H
Eris
Josette
J
Pascual
Julio
J
Whelchel
John
J
Magee
John C
JC
Campbell
Scott
S
Civati
Giovanni
G
Bourbigot
Bernard
B
Alves Filho
Gentil
G
Leone
John
J
Garcia
Valter Duro
VD
Rigotti
Paolo
P
Esmeraldo
Ronaldo
R
Cambi
Vincenzo
V
Haas
Tomas
T
Jappe
Annette
A
Bernhardt
Peter
P
Geissler
Johanna
J
Cretin
Nathalie
N
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
D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus