AUTHOR=Nourbakhsh Nima , Ekberg Jana , Skov Karin , Peters Christian Daugaard , Øzbay Aygen , Lindner Per , Buus Niels Henrik 

TITLE=Effects of Corticosteroid Treatment on Mycophenolic Acid Exposure in Renal Transplant Patients—Results From the SAILOR Study

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.742444

DOI=10.3389/fphar.2021.742444

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Mycophenolic acid (MPA) is a potent immunosuppressive agent used in solid organ transplantation. MPA exhibits large interindividual variation in dose-normalized plasma concentrations but is nevertheless usually prescribed as a fixed dose without use of therapeutic drug monitoring (TDM). Data on the effect of corticosteroid (CS) treatment on MPA concentrations during concomitant tacrolimus treatment remains sparse.</p><p><bold>Methods:</bold> Data is based on TDM of MPA area under the concentration curve (AUC) in 210 renal transplant recipients participating in the prospective, randomized, controlled, multi-center trial (SAILOR) where a steroid-free immunosuppressive regimen with mycophenolate mofetil (MMF) and low-dose tacrolimus was compared with a conventional prednisolone-based treatment regimen. Multilevel mixed-effects linear regression post-hoc analyses of MPA AUC was performed.</p><p><bold>Results:</bold> Median MPA AUC at baseline (within the first 2 weeks post-transplant) in patients taking 2 g MMF daily was 53 mg*h/L (interquartile range: 43–69 mg*h/L, min: 24—max: 117 mg*h/L). Between-patient variation in MPA AUC was up to 5-fold on the same MMF dose. Patients in the steroid-free group had 12.5% lower (95% CI; 3.2–20.9%, <italic>p</italic> = 0.01) MPA AUC levels at baseline compared to the steroid treated group. During follow-up (14 days–2 years post-transplant) there were no significant differences in MPA AUC between the groups with MPA AUC being 4.2% lower (95% CI: −4.8%−12,5%, <italic>p =</italic> 0.35) in the steroid-free <italic>vs</italic> standard treatment group in restricted analysis after multivariate adjustment for tacrolimus trough level, body weight, time after transplantation and MMF dose. MMF dose was positively correlated with MPA AUC (<italic>p</italic> &lt; 0.001) whereas body weight was negatively correlated with MPA AUC (<italic>p</italic> &lt; 0.001). MPA AUC was 0.4% (95% CI: 0.2–0.6%, <italic>p</italic> &lt; 0.001) lower per 1 kg increase in weight. Tacrolimus trough levels had no significant effect on MPA AUC.</p><p><bold>Conclusion:</bold> Immunosuppression with CS during concomitant tacrolimus treatment was shortly after transplantation associated with a significantly higher MPA exposure but the effect was small and not maintained during follow-up. Low body weight was associated with higher MPA exposure, which suggests a potential for weight adjusted MMF dosing.</p>