| Autor: |
Barten, Markus J., Hirt, Stephan W., Garbade, Jens, Bara, Christoph, Doesch, Andreas O., Knosalla, Christoph, Grinninger, Carola, Stypmann, Jörg, Sieder, Christian, Lehmkuhl, Hans B., Porstner, Martina, Schulz, Uwe, Deuse, Tobias, Costard‐Jaeckle, Angelika, Sill, Björn, Haneya, Assad, Eifert, Sandra, Kaczmarek, Ingo, Eickmeyer, Holm, Hiemann, Nicola, Kemper, Dagmar |
| Zdroj: |
American Journal of Transplantation; November 2019, Vol. 19 Issue: 11 p3006-3017, 12p |
| Abstrakt: |
In the 12‐month, open‐label MANDELAstudy, patients were randomized at month 6 after heart transplantation to (1) convert to calcineurin inhibitor (CNI)‐free immunosuppression with everolimus (EVR), mycophenolic acid and steroids (CNI‐free, n = 71), or to (2) continue reduced‐exposure CNI, with EVRand steroids (EVR/redCNI, n = 74). Tacrolimus was administered in 48.8% of EVR/redCNIpatients and 52.6% of CNI‐free patients at randomization. Both strategies improved and stabilized renal function based on the primary endpoint (estimated GFRat month 18 posttransplant postrandomization) with superiority of the CNI‐free group vs EVR/redCNI: mean 64.1 mL/min/1.73 m2vs 52.9 mL/min/1.73 m2; difference + 11.3 mL/min/1.73 m2(P< .001). By month 18, estimated GFRhad increased by ≥ 10 mL/min/1.73 m2in 31.8% and 55.2% of EVR/redCNIand CNI‐free patients, respectively, and by ≥ 25 mL/min/1.73 m2in 4.5% and 20.9%. Rates of biopsy‐proven acute rejection (BPAR) were 6.8% and 21.1%; all cases were without hemodynamic compromise. BPARwas less frequent with EVR/redCNIvs the CNI‐free regimen (P= .015); 6 of 15 episodes in CNI‐free patients occurred with EVRconcentration < 5 ng/mL. Rates of adverse events and associated discontinuations were comparable. EVR/redCNIfrom month 6 achieved stable renal function with infrequent BPAR. One‐year renal function can be improved by early conversion to EVR‐based CNI‐free therapy but requires close EVRmonitoring. Clinical trials registry: ClinicalTrials.gov NCT00862979. The 12‐month, randomized, open‐label MANDELA study shows that switching patients at 6 months after heart transplantation from standard immunosuppression to everolimus, mycophenolic acid, and steroids or to reduced‐exposure calcineurin inhibitor, everolimus, and steroids improves renal function in either case, but the enhanced renal benefit seen in the calcineurin inhibitor–free group requires close monitoring of everolimus exposure to avoid an increased risk of biopsy‐proven acute rejection. Tsay and Eisen comment in their editorial on page 2967. |
| Databáze: |
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