Everolimus (Certican) in renal transplantation: a review of clinical trial data, current usage, and future directions.

Abstract: The efficacy and tolerability of everolimus have been demonstrated in a number of clinical trials, and there is also an increasing body of clinical experience. The efficacy of everolimus after renal transplantation is at least equivalent to that of mycophenolate mofetil. Studies combining everolimus with full- or reduced-dose cyclosporine (CsA) have shown that CsA exposure can be minimized, without increasing the risk of acute rejection, particularly when combined with therapeutic drug monitoring. A role for everolimus in regimens involving elimination of calcineurin inhibitors is currently being investigated. Everolimus with significantly reduced-dose CsA has not been shown to enhance CsA-related nephrotoxicity. Adverse events seen in trials of everolimus are generally class-specific and include edema, arthralgia, dyslipidemia, impaired wound healing, and proteinuria. A low incidence of malignancy has been observed with everolimus, and studies are ongoing to examine its antitumor effects in the treatment of certain malignancies. It seems likely that everolimus will continue to play a role in the development of reduced-exposure calcineurin inhibitor regimens and has considerable potential to improve outcomes for transplant recipients, focused perhaps on “old-for-old” transplant recipients and patients at high risk of poor graft function or malignancy. This review considers the available data on the clinical application of everolimus and identifies current and future strategies for improving outcomes after renal transplantation. [Copyright &y& Elsevier]