Effect of corticosteroid withdrawal on tacrolimus and mycophenolate mofetil exposure in a randomized multicenter study.
Shihab FS, Lee ST, et al.American Journal of Transplantation. 2013; 13(2): 474-484
Aims
This was a sub-analysis of the Astellas Corticosteroid Withdrawal Trial, a 5-year, prospective, multicenter, randomized, double-blind study of early corticosteroid withdrawal in kidney transplant recipients. The sub-analysis investigated the clinical significance of the pharmacokinetic drug interaction between corticosteroids and tacrolimus but also dose adjustment of mycophenolate mofetil (MMF) in the setting of corticosteroid withdrawal.
Interventions
Early corticosteroid withdrawal versus continued corticosteroid use in combination with tacrolimus and MMF.
Participants
397 kidney transplant recipients.
Outcomes
Tacrolimus and MMF dose, tacrolimus trough levels, serum creatinine and potassium levels, cytomegalovirus disease (CMV) and CMV infection/syndrome and drug side-effects.
Follow-up
5 years
CET Conclusions
This is a sub study of the large Astellas corticosteroid withdrawal trial and shows that with corticosteroid withdrawal there is a significant impact on tacrolimus levels and also on mycophenolate levels, while serum creatinine is increased as is serum potassium. These are statistically significant differences but whether they are clinically significant is not clear.
Data analysis
Modified intention-to-treat analysis
Quality notes
Score based on Woodle, E., M. First, et al. (2008). "A prospective, randomized, double-blind, placebo-controlled multicenter trial comparing early (7 day) corticosteroid cessation versus long-term, low-dose corticosteroid therapy." Annals of Surgery 248(4): 564-577.
Trial registration
ClinicalTrials.gov - NCT00650468