Efficacy of everolimus with reduced-exposure cyclosporine in de novo kidney transplant patients at increased risk for efficacy events: analysis of a randomized trial.
J Nephrol
; 28(5): 633-9, 2015 Oct.
Article
in En
| MEDLINE
| ID: mdl-25708913
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Immunosuppression Therapy
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Kidney Transplantation
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Cyclosporine
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Everolimus
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Graft Rejection
Type of study:
Clinical_trials
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Etiology_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
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Adult
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Aged
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Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
J Nephrol
Journal subject:
NEFROLOGIA
Year:
2015
Document type:
Article
Affiliation country:
Italy