Mycophenolate Mofetil

Abstract

Most pharmacoeconomic studies of mycophenolate mofetil have focused on its use as part of maintenance immunosuppression for renal transplantation, involving short-term (3 to 12 months) time frames. In general, mycophenolate mofetil reduced the treatment costs for rejection episodes and graft failure which offset its higher drug acquisition cost compared with azathioprine. Several cost analyses have been modelled on the large multicentre trials of adult renal transplant recipients. The use of mycophenolate mofetil was associated with either cost savings or no additional costs after 6 or 12 months in French, US and Canadian analyses of triple or quadruple immunosuppressant therapy. A further cost analysis utilising a registry database of renal transplant recipients in the US found mycophenolate mofetil to be cost saving compared with azathioprine after 6.4 years when evaluating costs due to graft loss only. Of the limited cost-effectiveness analyses with the drug, one US study modelled the 1- and 10-year cost effectiveness of mycophenolate mofetil and various other immunosuppressants used in combined regimens. Long-term use of mycophenolate mofetil was less cost effective than other regimens, but the use of long-term mycophenolate mofetil in high-risk patients was shown to be a relatively cost-effective strategy. In another US analysis comparing mycophenolate mofetil with azathioprine as part of quadruple therapy, mycophenolate mofetil was associated with slightly lower costs during the first year after renal transplantation as well as improved clinical outcomes. Conclusion: Pharmacoeconomic studies support the use of mycophenolate mofetil as part of immunosuppressant therapy in renal transplantation, at least in the short term. Although the cost effectiveness of mycophenolate mofetil in the long term is less clear, limited pharmacoeconomic data available appear promising. Among issues to be examined in future economic analyses in renal transplantation are the calcineurin-sparing potential of mycophenolate mofetil and the feasibility of using more efficient mycophenolate mofetil dosage regimens when using the drug on a long-term basis. Additional pharmacoeconomic analyses of mycophenolate mofetil are also needed in other types of solid organ transplantation. Transplantation of a solid organ is a complex and expensive procedure. In the early to mid-1990s, the cost of renal transplantation for the first year in several European countries was about $US20 000 to $US30 000 per patient, and corresponding costs in the US were about 4-fold higher (≈$US100 000). Annual treatment costs beyond the first year were much lower (≈$US10 000 to $US15 000) and were broadly similar between these geographical regions, although still higher in the US. There are fewer cost data for other forms of organ transplant, but these procedures appear to be slightly more costly than renal transplants. Following transplantation, considerable costs continue to accrue due to maintenance immunosuppressive drug treatment, follow-up consultations and treatment of any complications. In the US, immunosuppressant agents account for approximately 83 to 84% of outpatient drug costs during the first 3 years after renal transplantation; outpatient drugs account for 35 to 43% of total healthcare expenditures during this period. Despite the high utilisation of healthcare resources, the costs of solid organ transplantation compare well with treatment of end-stage disease. In particular, renal transplants are the most cost-effective solid organ transplants, showing marked cost savings compared with dialysis treatment in various studies; however, this is an issue that requires ongoing scrutiny as costs for organ procurement, immunosuppression and other items continue to change. Any complications which may occur post-transplantation, such as rejection episodes, infections, and graft failure, will result in increased costs. To optimise clinical and economic outcomes in transplant recipients appropriate measures must be taken to minimise complications with good transplant procedures and optimal immunosuppressant therapy. The clinical benefits of mycophenolate mofetil as part of a maintenance immunosuppression regimen for renal transplant recipients have been clearly demonstrated in three large multicentre, randomised, controlled trials involving nearly 1500 adult renal transplant recipients. When used in combination with cyclosporin and corticosteroids, mycophenolate mofetil reduced the incidence of acute rejection by approximately 50% compared with azathioprine and by 70% compared with placebo. In addition, rejection episodes experienced by patients receiving mycophenolate mofetil tended to be less severe than those of patients receiving azathioprine or placebo. When the studies were extended to 3 years there appeared to be a general trend towards better graft and patient survival in patients receiving mycophenolate mofetil. These results are supported by those from large databases or registries of many thousands of renal transplant recipients. In the 1990s during a period of markedly increased use of mycophenolate mofetil, the risk of graft loss was reduced by 60% and the risk of death was halved compared with azathioprine. Mycophenolate mofetil was also found to decrease the relative risk for the development of chronic renal graft failure by 27%. The clinical efficacy of mycophenolate mofetil as maintenance immunosuppressive therapy has also been demonstrated in cardiac transplant recipients in a large multicentre, randomised, double-blind study comparing mycophenolate mofetil with azathioprine (both in combination with cyclosporin and corticoste-roids). At 3 years after transplantation, mycophenolate mofetil was associated with better graft survival than azathioprine (88.1 vs 81.6%) and a 36% relative reduction in patient mortality. A large multicentre, double-blind, randomised study in liver transplant recipients...