Alternatives to immediate release tacrolimus in solid organ transplant recipients: When the gold standard is in short supply

Given the current climate of drug shortages in the United States, this review summarizes available comparative literature on the use of alternative immunosuppressive agents in adult solid organ transplant recipients including kidney, pancreas, liver, lung, and heart, when immediate‐release tacrolimus (IR‐TAC) is not available. Alternative options explored include extended‐release tacrolimus (ER‐TAC) formulations, cyclosporine, belatacept, mammalian target of rapamycin inhibitors, and novel uses of induction therapy for maintenance immunosuppression. Of available alternatives, only ER‐TAC formulations are of non‐inferior efficacy compared to IR‐TAC when used de novo or after conversion in stable kidney transplant recipients (KTRs). All other alternatives were associated with higher rates of biopsy‐proven rejection, but improved tolerance from classic adverse effects of IR‐TAC including nephrotoxicity and development of diabetes. While most alternative therapies are approved in KTRs, access via third‐party payors is an obstacle in non‐KTRs. In the setting of IR‐TAC shortage, alternate therapeutic options may be plausible depending on the organ population and individual patient situation to ensure appropriate, effective immunosuppression for each patient.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156148/2/ctr13903.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156148/1/ctr13903_am.pd

Equivalence and interchangeability of narrow therapeutic index drugs in organ transplantation

The editorial services of iS Health, involved in the preparation of this manuscript, were supported by Astellas Pharma Europe Ltd

Biomarkers of Tolerance in Kidney Transplantation: Are We Predicting Tolerance or Response to Immunosuppressive Treatment?

We and others have previously described signatures of tolerance in kidney transplantation showing the differential expression of B cell-related genes and the relative expansions of B cell subsets. However, in all of these studies, the index group-namely, the tolerant recipients-were not receiving immunosuppression (IS) treatment, unlike the rest of the comparator groups. We aimed to assess the confounding effect of these regimens and develop a novel IS-independent signature of tolerance. Analyzing gene expression in three independent kidney transplant patient cohorts (232 recipients and 14 tolerant patients), we have established that the expression of the previously reported signature was biased by IS regimens, which also influenced transitional B cells. We have defined and validated a new gene expression signature that is independent of drug effects and also differentiates tolerant patients from healthy controls (cross-validated area under the receiver operating characteristic curve [AUC] = 0.81). In a prospective cohort, we have demonstrated that the new signature remained stable before and after steroid withdrawal. In addition, we report on a validated and highly accurate gene expression signature that can be reliably used to identify patients suitable for IS reduction (approximately 12% of stable patients), irrespective of the IS drugs they are receiving. Only a similar approach will make the conduct of pilot clinical trials for IS minimization safe and hence allow critical improvements in kidney posttransplant management