Pasternak Amy L, Marshall Vincent D, Gersch Christina L, Rae James M, Englesbe Michael, Park Jeong M
Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, 48109, USA.
Department of Internal Medicine, Michigan Medicine, Ann Arbor, MI, 48109, USA.
Pharmgenomics Pers Med. 2021 Mar 12;14:319-326. doi: 10.2147/PGPM.S285444. eCollection 2021.
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 genotype was predictive of healthcare resource utilization in pediatric renal and heart transplant recipients.
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 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 genotype was evaluated via univariate analysis for the first year and multivariable analysis at 30, 90, 180, 270, and 365 days post-transplant.
Eighty-five subjects were included, 48 renal transplant recipients and 37 heart transplant recipients. 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. genotype was not associated with rejection or DSA formation. Age and induction therapy were associated with higher total charges.
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.
基因型是个体间他克莫司血药浓度差异的重要影响因素，可能会影响移植患者达到治疗浓度所需的时间以及他克莫司剂量调整的次数。增加他克莫司治疗的调整可能意味着更高的医疗资源负担。本研究的目的是评估基因型是否可预测小儿肾移植和心脏移植受者的医疗资源利用情况。
纳入2014年6月1日至2018年12月31日期间接受肾移植或心脏移植且年龄小于18岁、采用以他克莫司为基础的免疫抑制治疗的患者。采集二次使用样本进行基因分型。从电子病历中回顾性收集临床数据。医疗资源利用指标包括剂量变化次数、他克莫司血药浓度检测次数、住院时间、临床就诊次数以及移植后第一年的总费用。还收集了移植后第一年内的排斥反应和供者特异性抗体（DSA）形成情况。通过单因素分析评估第一年基因型的影响，并在移植后30、90、180、270和36５天进行多因素分析。
共纳入85名受试者，其中48名肾移植受者和37名心脏移植受者。基因型与肾移植的任何结局均无关联，然而，CYP3A5表达型表型是心脏移植受者剂量变化更多、他克莫司血药浓度检测次数更多、住院时间更长以及总费用更高的预测因素。基因型与排斥反应或DSA形成无关。年龄和诱导治疗与总费用较高相关。
基因型可能预测移植后第一年的医疗资源利用情况，尽管这可能因他克莫司管理方式的差异而减轻。未来的研究应评估他克莫司基因型指导给药策略对医疗利用资源的影响。
