TACROLIMUS AND MMF IN CARDIAC TRANSPLANTATION: IMPORTANCE OF MYCOPHENOLIC ACID DRUG MONITORING

Abstract

745 Background: Tacrolimus and mycophenolate mofetil (MMF) are both potent immunosuppressants. Interest has recently been expressed in these two agents in a variety of transplant indications. To assess the efficacy of this combination as primary therapy following cardiac transplantation, the following study was undertaken. Methods: 45 patients (pts) were enrolled; 15 into phase I and 30 to phase II of the study. All patients were administered intravenous tacrolimus for a 2-3-day period post-transplant prior to conversion to oral therapy; target blood concentrations were 10-15 ng/mL. Treatment also consisted of steroids and MMF. A fixed dose of 2 g/day MMF was given during phase I whilst MMF doses were adjusted according to mycophenolic acid (MPA) blood levels during phase II (target range 2.5-4.5µg/mL). Mean follow-up was 554±61 days and 305±74 days for phase I and II, respectively. Findings: Phase I. Pt survival was 100%. Acute rejection episodes (ARE) were diagnosed in 66.7% of pts(ARE/pt: 1.33 ± 1.18). Mean MPA blood levels in excess of 3.0µg/mL were associated with freedom from rejection. Phase II. One pt died from aspergillosis resulting in a survival rate of 96.7%. Rejection was evident in 10.0% of pts (ARE/pt: 0.1±0.3); mean MPA trough levels were 1.0+0.3 µg/mL in these 3 pts at the time. All 3 cases resolved following pulse steroid therapy. Steroids were successfully withdrawn from all pts after 6 months treatment. Conclusions: Combination therapy with tacrolimus and MMF is associated with suppression of acute myocardial rejection; this is dependent upon doses of both drugs being adjusted in accordance with their respective target blood concentrations. Routine MPA blood monitoring appears to result in a marked improvement in clinical efficacy. This strategy also allows complete withdrawal of steroids as early as 6 months after HTx.