Efficacy of everolimus with reduced-exposure cyclosporine in de novo kidney transplant patients at increased risk for efficacy events: analysis of a randomized trial.

Abstract

The efficacy of de novo everolimus with reduced-exposure calcineurin inhibitor (CNI) was examined in kidney transplant subpopulations from the A2309 study that were identified to be at increased risk for efficacy events. A2309 was a 24-month, multicenter, open-label trial in which 833 de novo kidney transplant recipients were randomized to everolimus targeting 3-8 or 6-12 ng/ml with reduced-exposure cyclosporine (CsA), or mycophenolic acid (MPA) with standard-exposure CsA, all with basiliximab induction. The composite efficacy endpoint was treated biopsy-proven acute rejection (BPAR), graft loss, death, or loss to follow-up. Cox proportional hazard modeling showed male gender, younger recipient age, black race, delayed graft function, human leukocyte antigen (HLA) mismatch ≥3 and increasing donor age to be significantly predictive for the composite efficacy endpoint at months 12 or 24 post-transplant. CsA exposure was 53-75 % lower, and 46-75 % lower, in patients receiving everolimus 3-8 ng/ml or receiving everolimus 6-12 ng/ml, respectively, versus MPA-treated patients. The incidence of the composite endpoint was similar in all three treatment groups within each subpopulation analyzed. The incidence of treated BPAR was similar with everolimus 3-8 ng/ml or MPA in all subpopulations, but less frequent with everolimus 6-12 ng/ml versus MPA in patients with HLA mismatch ≥3 (p = 0.049). This post hoc analysis of a large, randomized trial suggests that a de novo regimen of everolimus with reduced-exposure CsA maintains immunosuppressive efficacy even in kidney transplant patients at increased risk for efficacy events despite substantial reductions in CsA exposure.

• Authors: Mario Carmellini, Valter Garcia, Zailong Wang, Marcela Vergara, Graeme Russ
• Journal: Journal of nephrology (J Nephrol) Vol. 28 Issue 5 Pg. 633-9 (Oct 2015) ISSN: 1724-6059 [Electronic] Italy
• PMID: 25708913 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Immunosuppressive Agents
• Cyclosporine
• Everolimus

Topics

• Adolescent
• Adult
• Aged
• Biopsy
• Cyclosporine (administration & dosage)
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Everolimus (administration & dosage)
• Female
• Follow-Up Studies
• Graft Rejection (drug therapy, pathology)
• Humans
• Immunosuppression Therapy (methods)
• Immunosuppressive Agents (administration & dosage)
• Kidney (pathology)
• Kidney Failure, Chronic (surgery)
• Kidney Transplantation (adverse effects)
• Male
• Middle Aged
• Risk Factors
• Time Factors
• Treatment Outcome
• Young Adult