Switching from calcineurin inhibitors to Mammalian target of rapamycin inhibitors--finally caught the right wave?

摘要

Since approval by the Food and Drug Administration and European Medicines Agency in 1999-2001 of sirolimus and by the Food and Drug Administration in 2010 of everolimus, the position of mammalian target of rapamycin (mTOR) inhibitors in immunosuppressive regimens for renal transplantation has been a matter of much research and debate. Only 6.1% of kidney transplant recipients are taking an mTOR inhibitor at 1 year after transplantation (1). The reason for this is not to be found in failed marketing strategies but in difficulties to establish the long-term benefits, the best dosing strategy and the appropriate timing of introduction of mTOR inhibitors. Studies on the use of mTOR inhibitors in de novo immunosuppression, at time of transplantation, showed a poor risk-benefit profile (2-7). Substituting an mTOR inhibitor for a calcineurin inhibitor (CNI) at later stages after transplantation did not lead to the hoped effect (8,9).