Corticosteroid-Sparing and Optimization of Mycophenolic Acid Exposure in Liver Transplant Recipients Receiving Mycophenolate Mofetil and Tacrolimus: A Randomized, Multicenter Study.
Saliba F, Rostaing L, et al.Transplantation 2016; 100(8): 1705-1713.
Aims
To examine the efficacy and tolerance of a corticosteroid (CS)-free regimen with tacrolimus (Tac) and dose-intensified mycophenolate mofetil (MMF).
Interventions
Participants were randomised to receive either CS-free regimen with MMF dose adjusted based on mycophenolic acid (MPA) total exposure since day 5 (Arm A), compared to fixed dose MMF, Tac and CS up to 6 months post-transplantation (Arm B).
Participants
174 recipients of a first orthotopic liver transplant from a deceased or living donor, aged ≥ 18 years.
Outcomes
The primary outcome measured was the incidence of biopsy proven acute rejection. Secondary measured outcomes included all acute rejection episodes, graft and patient survival and histological evaluation of the graft from liver biopsies.
Follow-up
12 months
CET Conclusions
This study compares a standard tacrolimus/MMF/corticosteroid protocol with a steroid free protocol using higher-dose MMF and MPA monitoring in liver transplant recipients. The authors report that BPAR rates are similar in both arms, with the intense MMF group experiencing more leukopenia and the corticosteroid group experiencing a higher rate of post-transplant diabetes. These results are perhaps unsurprising, and there are some limitations. The absence of control arms without either MPA monitoring or intensified MMF dosing mean that it is unclear whether similar results could be achieved with just intensified MMF dosing, MPA monitoring, or in fact neither with just steroid avoidance. Compliance with dose recommendations, as is common in studies like this, was poor. It is unclear from the manuscript whether there was any significant difference between the MMF exposures seen between the groups, but it would appear not. Finally, the study was powered as a non-inferiority design with a maximum clinically-significant difference in BPAR of 15% - a quite large difference when the baseline BPAR rate is only 9%. Despite the conservative sample-size calculation, the study only recruited 174 of the required 224 patients to the per protocol population (77%), with no explanation provided.
Data analysis
Modified intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT00545402