The utility of simultaneous quadruple immunosuppression (triple immunosuppression with induction therapy) in LRD renal transplant recipients is highly debatable. These patients already benefit from good short- and long-term results, together with reductions in delayed graft function, ischemic injury, and primary non-functioning grafts.
In our retrospective study, patients did not receive additional benefit with BAS. The agent had no impact on either rejection rates or time to first rejection. Nor was it associated with cost-savings in initial hospitalizations, readmissions, or infections. These findings were maintained when accounting for several outliers.
The cost-benefit of BAS and daclizumab was determined by applying the results of an international study group to a database of Canadian health system costs.[7,9] The study included cadaveric donors receiving dual immunosuppression with cyclosporine microemulsion and steroids. Based on rejection rates of 52.2% and 34.2% in the placebo and BAS groups, respectively, the authors estimated an annual cost saving of $1554 (Canadian)/patient with BAS therapy. When converted at 1999 exchange rates for the U.S. dollar, that equals approximately $1045. Statistical significance was not determined. A dual immunosuppressive regimen in a cadaveric donor group accounts for higher rejection rates and more pronounced benefit from the addition of a third immunosuppressant compared with our patients, with low probability for rejection and a triple-drug regimen. Discrepancies in savings may have occurred because of differences between the institutional Canadian and privatized United States health care systems.
In an economic analysis of one trial, subgroup analysis data showed a 28% rejection rate in living donors receiving immunosuppression with cyclosporine microemulsion and steroids. The double-drug regimen in this more diverse population may account for their high rejection rate and makes comparison between them and our patients difficult. Overall, 1-year overall medical costs and hospital costs for treating acute rejection were lower in patients treated with BAS. Median hospitalization was 1 day shorter, and the difference in its cost was over $1400 lower in BAS recipients. This may be attributed to a 31% reduction in acute rejection rates and 47% reduction in hospitalizations in these cadaveric and living donor transplant recipients. As expected with our results, no benefit was seen due to lack of rejection rate reduction or decreased infection rates.
Our patients began receiving cyclosporine and azathioprine 3 days before scheduled transplantation. This therapy may negate the need for antibody induction as cyclosporine would be at or near steady-state levels. Induction with a calcineurin-sparing agent was not considered given the overwhelming prevalence of excellent primary function in the new graft even with pretransplantation cyclosporine. Regardless, BAS was administered to improve acute rejection rates above our average rate at that time.
Demographically, BAS recipients had several characteristics reported as potential risk factors for increased rejection. The group had significantly more female than male donors, and three of four patients rejecting were male recipients of female donors. Disparity between female donors and male recipients is thought to influence graft outcome negatively. The BAS group also had a greater number of patients receiving dialysis before transplantation. A review of the U.S. Renal Data System found increasing duration of dialysis to be an increased risk of rejection within the first 6 months after transplantation. The BAS group also had more high-risk patients with CMV-positive serology, but only one more patient with the disease. The disease or symptomatic infection, but not serology, influences rejection rates. Only one patient with rejection in the control group developed CMV disease 6 weeks after treatment for rejection. Therefore, there was no correlation in our groups between CMV disease and frequency of rejection during or after infection.
Our study lacked sufficient power to detect a difference in acute rejection rates. To detect a decrease of 10% in the BAS group at 80% power, each group would require 140 patients. Although our primary end point lacked sufficient power, significance was still achieved in initial hospitalization costs, with a difference that exceeded the sole cost of BAS and its administration.
Infectious and malignant complications were not increased with BAS therapy. The effect of induction immunosuppression on this risk is questionable. The long-term level of immunosuppression may be more strongly associated with increases in infections and malignancy than the level of immunosuppression at a single time.[27,28] Most infections and malignancies were reported with the monoclonal muromonab-CD3 antibody and not other polyclonal agents.[9,10,29,30,31]
Patients treated with BAS, however, did have increased costs associated with infectious episodes. These may be attributed to additional CMV infections and greater administration of fluoroquinolones for urinary tract infections. In addition, all CMV infections in that group were treated for 12 weeks; only one control patient with CMV infection received a 12-week course, and the other received only 6 weeks of treatment. This shorter treatment would contribute to lower total drug cost for controls.
No adverse effects were associated with BAS. The IL-2R antagonist safety profile, as found in this study and others, may be seen as a significant advantage over lymphocytic antibody preparations.
Pharmacotherapy. 2003;23(4) © 2003 Pharmacotherapy Publications
Copyright © 1999, Pharmacotherapy Publications, Inc., All rights reserved.
Cite this: Lack of Economic Benefit With Basiliximab Induction in Living Related Donor Adult Renal Transplant Recipients - Medscape - Apr 01, 2003.