Cost-effective Immunosuppressive Options for Solid Organ Transplantation: A Guide to Lower Cost for the Renal Transplant Recipient in the USA Immunotherapy. 2010;2(6):879-888.
Abstract Of the numerous risks associated with immunotherapy for the prevention of rejection, cost is perhaps the most universal. In the USA and some other countries, the costs of immunosuppression make transplantation unavailable for some medically viable transplant candidates, and for others who receive a transplant, the long-term costs are economically crippling. Minimization and tapering of immunosuppression, use of generics, manipulation of metabolism, infection surveillance instead of prophylaxis, and advantageous routes of administration are some strategies that can be employed to reduce immunotherapy expense. Using these strategies, we describe an immunosuppression regimen for kidney transplantation that might be only a third of the cost of current 'standard' regimens in the USA. Such a regimen might allow some patients who might not otherwise qualify economically to safely receive a kidney transplant. The purpose of creating an alternative, lower-cost immunotherapy regimen is to give patients a choice. Responsible stewardship of scarce donor organs is the primary, and clearly appropriate, limiting factor.
Introduction Solid organ transplantation is one of the remarkable achievements of modern medicine. Patient and kidney graft survival rates at 1 year exceed 95% after living donor kidney transplantation, and life expectancy is substantially increased compared with those patients who remain on dialysis.[1–3] Replacement of lost organ function by transplantation clearly increases longevity and improves quality of life, but at the cost of requisite immunosuppression to prevent allograft rejection. Effective immunosuppression has numerous side effects, including nephrotoxicity, diabetes, anemia, cytopenias, hypertension, neuropathy and manifestations of over immunosuppression, such as infection and malignancy. However, one of the most universal complications of immunosuppressive drugs used in current protocols for solid organ transplantation is the economic burden placed on graft recipients. In the USA, the cost of immunosuppressive drugs and the monitoring required by their administration has been estimated at more than US$30,000 in the first year after transplantation, and approximately US$15,000 per year thereafter.[101] For some potential transplant candidates, the cost of immunosuppression is prohibitive to the medical benefits of transplantation.
A Potential Low-cost Immunotherapy Regimen for Kidney Transplantation The design of a cost-effective immunotherapy regimen would include at least some of the strategies discussed above; surveillance (rather than prophylaxis), use of generics, metabolic manipulation, advantageous use of efficient routes of administration and drug minimization. Table 1 shows the average wholesale price (AWP) of many of the individual drugs that make up the typical immunotherapy regimen for kidney and pancreas transplantation. The most commonly used immunosuppressive regimen includes a brand CNI, MPA, and anti-infectives, including valganciclovir ( Table 3 ). The annual cost of this 'standard' regimen (based on AWP) is approximately US$30,000. Although many current immunosuppression protocols aim to eliminate steroids, prednisone is the least expensive immunotherapeutic agent commonly used in solid organ transplantation ( Table 1 & Table 2 . The overall cost of transplantation might actually be reduced by steroid avoidance, as suggested by Gheith.[43] However, if the ability to receive a transplant is an economic choice based on the cost of the medical regimen to the patient, then use of steroids should be considered. Of the antimetabolites, AZA is by far the least expensive ( Table 1 & Table 2 . Use of AZA instead of MPA derivatives would significantly lower the cost of maintenance immunosuppression compared with standard regimens ( Table 2 , Table 3 & Table 4 ), but might come at a cost in efficacy as suggested by the meta-analysis of studies comparing AZA versus MPA-containing regimens (see earlier). In a randomized study of delayed conversion of MPA to AZA in a sirolimus-based immunotherapy regimen, El-Agroudy found a low risk of acute rejection and substantial cost savings.[44] However, initial use of AZA, instead of MPA, might be reasonable (as compared with current steroid-free regimens) if combined with steroid and a CNI ( Table 4 ). Addition of a T-cell-depleting induction agent, such as alemtuzumab, might further reduce the risk of acute rejection. Recipients at low immunological risk for rejection (low panel reactive antibody titres [PRA], primary kidney transplant only) commonly receive the standard, but expensive, immunotherapy protocol (i.e., CNI and MPA) and an IL-2 receptor-blocking induction agent. No studies have compared this 'high-cost' regimen to a lower-cost regimen of T-cell depletion (alemtuzumab), CNI, AZA and steroid. Other components of a cost-conscious immunotherapy regimen might include Bactrim (if not allergic) and ketoconazole (to boost CNI levels and allow lower CNI doses). Patients who demonstrate immunity to CMV (CMV IgG-positive) could be monitored for CMV infection rather than receive prophylaxis with valganciclovir, and fungal infection could also be treated if it should occur. Based upon AWP, a regimen containing TAC, AZA, prednisone, ketoconazole and Bactrim would be less than a third of the expense of current standard regimens, if all outcomes from its use were similar; a prospect that would require empiric comparison.
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