Long-term clinical impact of adaptation of initial tacrolimus dosing to CYP3A5 genotype.
Pallet N, Etienne I, et al.American Journal of Transplantation 2016;16(9):2670-5.
Aims
To retrospectively analyse the long-term clinical impact of adaptation of initial tacrolimus dosing according to CYP3A5 genotype, using the results of the Tactique study*.
Interventions
Participants of the Tactique study were randomly assigned at day 7 posttransplantation to receive tacrolimus at either a fixed dosage of 0.2 mg/kg/day (control group) or a dosage determined by their genotype (adapted-dose group).
Participants
212 patients analyzed in the intention to-treat population of the Tactique study, and for whom the graft and/or life status was available at the date of September 1, 2015.
Outcomes
The primary outcome measured was the incidence of graft loss over time. Secondary outcomes were incidence of biopsy-proven acute rejection, patient death, cardiovascular events, cancers, infections, proteinuria, graft function, and glycated haemoglobin.
Follow-up
Up to 85 months on average
CET Conclusions
Tacrolimus, a calcineurin inhibitor, is a key component of most modern immunosuppression protocols in kidney transplantation. It is known that adaptation of the daily dose of Tacrolimus to the CYP3A5 genotype is associated with the achievement of target trough concentrations of Tacrolimus. In this study the authors have retrospectively analysed patients from Tactique, which was a prospective multi-centre trial conducted in 2006 and 2007 to evaluate whether adaptation of Tacrolimus dosage according to the genotype would allow earlier achievement of ideal Tacrolimus trough levels. This certainly proved to be the case but in this long-term follow-up study over 5 years there was no difference in the incidence of biopsy proven acute rejection or graft survival between the control and the genotypically adapted Tacrolimus dose group. Nor was there any difference in death, cancer, cardiovascular events and infections between the two groups, and renal function was the same in both groups. The authors conclude that optimisation of the initial Tacrolimus dose using pharmacogenetic testing does not improve clinical outcomes.
Data analysis
Modified intention-to-treat analysis
Quality notes
Previously reported as *Thervet E, et al. Optimization of initial tacrolimus dose using pharmacogenetic testing. Clin Pharmacol Ther 2010; 87: 721–726.
Trial registration
None