Increased incidence of allograft rejection in stable heart transplant recipients after late conversion from mycophenolate mofetil to azathioprine

Mycophenolate mofetil (MMF) is a safe and effective immunosuppressive agent in kidney and liver transplantation. preliminary studies also support its use in heart transplantation. However, the cost of MMF is substantially gre ater than azathioprine (AZA), the current alternative. Since the majority o f rejection episodes occur within the first few months of transplantation, using MMF early after transplantation and subsequently converting to AZA, a fter the risk of rejection has diminished, might be cost-effective. In orde r to evaluate the safety of such a strategy in heart transplant recipients, we reviewed the rejection profiles of a group of patients who were convert ed from MMF to AZA late after transplantation. Forty-three stable patients on chronic MMF therapy as parr of an open-label , long-term safety study were converted to either commercially available MM F (CellCept(R)) or AZA, at the conclusion of the study. Demographic variabl es, rejection histories before and after conversion, and immunosuppressive regimens were examined. Twenty-three patients were continued on commercial MMF and 20 were converted to AZA therapy. The average duration of MMF thera py prior to conversion was 41 months in each group. Baseline demographics w ere similar in the two groups. Treated allograft rejection occurred in 10 o f 20 patients converting to AZA, as compared to only 1 of 23 patients remai ning on MMF; p = 0.002. Additionally, mean scores (1-5 scale) for the three biopsies before and after conversion favored continued MMF therapy (1.5 +/ - 0.6 before and 1.2 +/- 0.4 after conversion in MMF group vs. 1.3 +/- 0.5 before and 1.7 +/- 0.9 after conversion to AZA; p = 0.02). No allograft los s occurred as a result of conversion. These data suggest that conversion from MMF to AZA, even late after transpl antation, can be associated with allograft rejection. The costs associated with these rejection episodes (the additional immunosuppressive agents, end omyocardial biopsies, and physician visits) may exceed the potential cost s avings of converting stable heart transplant recipients from MMF to AZA.