Individualized Mycophenolate Mofetil Dosing Based on Drug Exposure Significantly Improves Patient Outcomes After Renal Transplantation |
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Authors: | Y Le Meur M Büchler A Thierry S Caillard F Villemain S Lavaud I Etienne P-F Westeel B H de Ligny L Rostaing E Thervet J C Szelag J-P Rérolle A Rousseau G Touchard P Marquet |
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Institution: | Department of Nephrology, University Hospital, Limoges, France. yannick.lemeur@chu-brest.fr |
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Abstract: | Efficacy and safety of mycophenolate mofetil (MMF) may be optimized with individualized doses based on therapeutic monitoring of its active metabolite, mycophenolic acid (MPA). In this 12-month study, 137 renal allograft recipients from 11 French centers receiving basiliximab, cyclosporine A, MMF and corticosteroids were randomized to receive either concentration-controlled doses or fixed-dose MMF. A novel Bayesian estimator of MPA AUC based on three-point sampling was used to individualize doses on posttransplant days 7 and 14 and months 1, 3 and 6. The primary endpoint was treatment failure (death, graft loss, acute rejection and MMF discontinuation). Data from 65 patients/group were analyzed. At month 12, the concentration-controlled group had fewer treatment failures (p = 0.03) and acute rejection episodes (p = 0.01) with no differences in adverse event frequency. The MMF dose was higher in the concentration-controlled group at day 14 (p < 0.0001), month 1 (p < 0.0001) and month 3 (p < 0.01), as were median AUCs on day 14 (33.7 vs. 27.1 mg*h/L; p = 0.0001) and at month 1 (45.0 vs. 30.9 mg*h/L; p < 0.0001). Therapeutic MPA monitoring using a limited sampling strategy can reduce the risk of treatment failure and acute rejection in renal allograft recipients 12 months posttransplant with no increase in adverse events. |
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Keywords: | Area-under-curve mycophenolate mofetil renal transplantation therapeutic drug monitoring |
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