Interleukin-2 receptor antagonist therapy leads to increased tacrolimus levels after kidney transplantation

Authors

Sonia Lin, University of Colorado Hospital Denver
Alice K. Henning, The EMMES Corporation
Fatemeh Akhlaghi, University of Rhode Island
Robin Reisfield, Astellas Pharma US, Inc.
Andrea Vergara-Silva, Ziopharm Oncology Inc.
M. Roy First, Astellas Pharma US, Inc.

Document Type

Article

Date of Original Version

4-25-2015

Abstract

Background: Tacrolimus (TAC) is a known substrate for cytochrome P450 (CYP) enzyme. CYP enzyme activity can be modulated by activation of IL-2 receptors (IL-2R) expressed on hepatocytes and intestinal cells. IL-2R antagonists (IL-2RA) may promote preferential binding of circulating IL-2 to IL-2Rs on these cells by blocking IL-2Rs on activated T cells. This downregulates CYP enzymes, leading to increased calcineurin inhibitor levels. This analysis evaluates the significance of this drug-drug interaction in kidney transplant recipients. Methods: Data were used from a previous 5-year randomized, controlled study comparing outcomes associated with maintenance immunosuppression using 2 corticosteroid regimens: long-term therapy versus early withdrawal. Patients received either IL-2RAs or rabbit anti-thymocyte globulin (rATG) for induction. Serial TAC trough levels and doses were compared between induction agents within each corticosteroid arm. Rejection rates, patient/graft survival, and TAC adverse effects were also evaluated. Results: In the first week, IL-2RA-treated patients achieved significantly higher trough levels and required lower doses (in milligram per kilogram) to achieve target levels than rATG-treated patients. No significant differences in rejection rates, patient/graft survival, or rate of adverse effects were observed through 1 year.

Publication Title, e.g., Journal

Therapeutic Drug Monitoring

Volume

37

Issue

2

Citation/Publisher Attribution

Lin, Sonia, Alice K. Henning, Fatemeh Akhlaghi, Robin Reisfield, Andrea Vergara-Silva, and M. R. First. "Interleukin-2 receptor antagonist therapy leads to increased tacrolimus levels after kidney transplantation." Therapeutic Drug Monitoring 37, 2 (2015). doi: 10.1097/FTD.0000000000000125.