Impact of CYP3A5 phenotype on tacrolimus time in therapeutic range and clinical outcomes in pediatric renal and heart transplant recipients.

STUDY OBJECTIVE

This study investigated the effect of CYP3A5 phenotype on time in therapeutic range (TTR) of tacrolimus post-transplant in pediatric patients.

DESIGN AND DATA SOURCE

This retrospective study assessed medical records of pediatric kidney and heart recipients with available CYP3A5 genotype for tacrolimus dosing, troughs, and the clinical events (biopsy-proven acute rejection [BPAR] and de novo donor-specific antibodies [dnDSA]).

MEASUREMENTS AND MAIN RESULTS

The primary outcome, mean TTR in the first 90 days post-transplant, was 9.0% (95% CI: -16.1, -1.9) lower in CYP3A5 expressers (p = 0.014) when adjusting for time to therapeutic concentration and organ type. There was no difference between CYP3A5 phenotypes in time to the first clinical event using TTR during the first 90 days. When applying TTR over the first year, there was a significant difference in event-free survival (EFS) which was 50.0% for CYP3A5 expressers/TTR < 35%, 45.5% for expressers/TTR ≥ 35%, 38.1% for nonexpressers/TTR < 35%, and 72.9% for nonexpressers/TTR ≥ 35% (log-rank p = 0.03). A post hoc analysis of EFS identified CYP3A5 expressers had lower EFS compared to nonexpressers in patients with TTR ≥ 35% (p = 0.04) but no difference among patients with TTR < 35% (p = 0.6).

CONCLUSIONS

The relationship between TTR and CYP3A5 phenotype suggests that achieving a TTR ≥ 35% during the first year may be a modifiable factor to attenuate the risk of BPAR and dnDSA.