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. 2021 Mar 12:14:319-326.
doi: 10.2147/PGPM.S285444. eCollection 2021.

Evaluating the Impact of CYP3A5 Genotype on Post-Transplant Healthcare Resource Utilization in Pediatric Renal and Heart Transplant Recipients Receiving Tacrolimus

Amy L Pasternak  1 , Vincent D Marshall  1 , Christina L Gersch  2 , James M Rae  2 , Michael Englesbe  3 , Jeong M Park  1
Affiliations

Evaluating the Impact of CYP3A5 Genotype on Post-Transplant Healthcare Resource Utilization in Pediatric Renal and Heart Transplant Recipients Receiving Tacrolimus

Amy L Pasternak et al. Pharmgenomics Pers Med. .

Abstract

Purpose: CYP3A5 genotype is a significant contributor to inter-individual tacrolimus exposure and may impact the time required to achieve therapeutic concentrations and number of tacrolimus dose adjustments in transplant patients. Increased modifications to tacrolimus therapy may indicate a higher burden on healthcare resources. The purpose of this study was to evaluate whether CYP3A5 genotype was predictive of healthcare resource utilization in pediatric renal and heart transplant recipients.

Patients and methods: Patients <18 years of age with a renal or heart transplant between 6/1/2014-12/31/2018 and tacrolimus-based immunosuppression were included. Secondary use samples were obtained for CYP3A5 genotyping. Clinical data was retrospectively collected from the electronic medical record. Healthcare resource utilization measures included the number of dose changes, number of tacrolimus concentrations, length of stay, number of clinical encounters, and total charges within the first year post-transplant. Rejection and donor-specific antibody (DSA) formation within the first year were also collected. The impact of CYP3A5 genotype was evaluated via univariate analysis for the first year and multivariable analysis at 30, 90, 180, 270, and 365 days post-transplant.

Results: Eighty-five subjects were included, 48 renal transplant recipients and 37 heart transplant recipients. CYP3A5 genotype was not associated with any outcomes in renal transplant, however, a CYP3A5 expresser phenotype was a predictor of more dose changes, more tacrolimus concentrations, longer length of stay, and higher total charges in heart transplant recipients. CYP3A5 genotype was not associated with rejection or DSA formation. Age and induction therapy were associated with higher total charges.

Conclusion: CYP3A5 genotype may predict healthcare resource utilization in the first year post-transplant, although this may be mitigated by differences in tacrolimus management. Future studies should evaluate the impact of genotype-guided dosing strategies for tacrolimus on healthcare utilization resources.

Keywords: cost of care; pediatric transplant; pharmacogenetics.

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Conflict of interest statement

Dr Amy L Pasternak and Dr Jeong M Park report grant funding from the National Center for Advancing Translational Sciences (NCATS) to support this work under award number: UL1TR002240. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Inclusion of eligible patients.
Figure 2
Figure 2
Impact of CYP3A5 phenotype on biopsy proven acute rejection (BPAR) or de novo donor-specific antibody (DSA) formation within the first year of transplant in kidney transplant recipients. The time to the composite outcome of BPAR or DSA did not differ significantly between CYP3A5 phenotype groups in renal transplant recipients.
Figure 3
Figure 3
Impact of CYP3A5 phenotype on biopsy proven acute rejection (BPAR) or de novo donor-specific antibody (DSA) formation within the first year of transplant in heart transplant recipients. The time to the composite outcome of BPAR or DSA did not differ significantly between CYP3A5 phenotype groups in heart transplant recipients.
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