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  • Title: Maintenance immunosuppression with intermittent intravenous IL-2 receptor antibody therapy in renal transplant recipients.
    Author: Gabardi S, Catella J, Martin ST, Perrone R, Chandraker A, Magee CC, McDevitt-Potter LM.
    Journal: Ann Pharmacother; 2011 Sep; 45(9):e48. PubMed ID: 21811001.
    Abstract:
    OBJECTIVE: To report what we believe to be the first 2 cases of long-term (>24 months) intermittent intravenous interleukin-2 receptor antibody (IL-2RA) therapy for maintenance immunosuppression following renal transplantation. CASE SUMMARY: The first patient is a 52-year-old female with a history of intolerance to calcineurin inhibitors (CNIs) and sirolimus. Following her second transplant, the patient received mycophenolate mofetil 100 mg twice daily, a tapering corticosteroid regimen (initial dose of methylprednisolone 500 mg tapered over 1 week to prednisone 30 mg/day), and biweekly intravenous daclizumab 1-1.2 mg/kg/dose; 33 months after transplant the IL-2RA was changed to intravenous basiliximab 40 mg once a month. At 40 months after transplant, the patient continued to have stable renal function (estimated glomerular filtration rate 48 mL/min/1.73 m²) with excellent tolerability. The second patient is a 59-year-old female also intolerant to CNIs and sirolimus who required intermittent maintenance therapy with intravenous basiliximab 20 mg/dose. Despite an initial rejection episode, the patient tolerated more than 2 years of basiliximab therapy with good renal function (estimated glomerular filtration rate 103 months after transplant 69 mL/min/1.73 m²) and no adverse events. DISCUSSION: The IL-2RAs basiliximab and daclizumab possess several characteristics of ideal maintenance immunosuppressive agents (ie, nondepleting, long half-lives, limited adverse events). Based on a MEDLINE search (through December 31, 2010) using the search terms basiliximab, daclizumab, organ transplant, immunosuppression, and/or maintenance immunosuppression, and an advanced search in the published abstracts from the American Transplant Congress and World Transplant Congress (2000-2010), it appears that IL-2RAs have been used successfully as short-term therapy in both renal and extrarenal transplant recipients to allow for renal recovery following CNI-induced nephrotoxicity. In heart transplant recipients, the IL-2RAs have been used for <24 months as maintenance immunosuppression in patients intolerant of CNIs or sirolimus. CONCLUSIONS: To the best of our knowledge, these 2 cases are the first to demonstrate that IL-2RAs can be used as an alternative to a CNI in a de novo immunosuppressive regimen. Also, this is the first report to illustrate successful long-term use of IL-2RAs in renal transplant recipients. This alternative approach was well tolerated by our patients, with no apparent adverse events. Although the efficacy of such regimens cannot be determined with 2 case reports, the fact that intermittent intravenous IL-2RA administration was successfully accomplished in these patients provides impetus to evaluate this treatment modality in prospective studies.
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