Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA.
Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA.
Pharmacogenomics J. 2024 May 15;24(3):14. doi: 10.1038/s41397-024-00334-1.
The objective of this study was to estimate the cost-effectiveness of CYP3A5 genotype-guided tacrolimus dosing in kidney, liver, heart, and lung transplant recipients relative to standard of care (SOC) tacrolimus dosing, from a US healthcare payer perspective. We developed decision-tree models to compare economic and clinical outcomes between CYP3A5 genotype-guided and SOC tacrolimus therapy in the first six months post-transplant. We derived inputs for CYP3A5 phenotype frequencies and physician use of genotype test results to inform clinical care from literature; tacrolimus exposure [high vs low tacrolimus time in therapeutic range using the Rosendaal algorithm (TAC TTR-Rosendaal)] and outcomes (incidences of acute tacrolimus nephrotoxicity, acute cellular rejection, and death) from real-world data; and costs from the Medicare Fee Schedule and literature. We calculated cost per avoided event and performed sensitivity analyses to evaluate the robustness of the results to changes in inputs. Incremental costs per avoided event for CYP3A5 genotype-guided vs SOC tacrolimus dosing were $176,667 for kidney recipients, $364,000 for liver recipients, $12,982 for heart recipients, and $93,333 for lung recipients. The likelihood of CYP3A5 genotype-guided tacrolimus dosing leading to cost-savings was 19.8% in kidney, 32.3% in liver, 51.8% in heart, and 54.1% in lung transplant recipients. Physician use of genotype results to guide clinical care and the proportion of patients with a high TAC TTR-Rosendaal were key parameters driving the cost-effectiveness of CYP3A5 genotype-guided tacrolimus therapy. Relative to SOC, CYP3A5 genotype-guided tacrolimus dosing resulted in a slightly greater benefit at a higher cost. Further economic evaluations examining intermediary outcomes (e.g., dose modifications) are needed, particularly in populations with higher frequencies of CYP3A5 expressers.
本研究旨在从美国医疗支付方的角度评估 CYP3A5 基因型指导的他克莫司剂量与标准护理（SOC）相比，在肾、肝、心和肺移植受者中的成本效益。我们开发了决策树模型，以比较 CYP3A5 基因型指导与 SOC 他克莫司治疗在移植后前 6 个月的经济和临床结果。我们从文献中获得了 CYP3A5 表型频率和医生使用基因型检测结果来为临床护理提供信息的输入；从真实世界数据中获得了他克莫司暴露（使用 Rosendaal 算法的高与低他克莫司治疗窗时间（TAC TTR-Rosendaal））和结果（急性他克莫司肾毒性、急性细胞排斥和死亡的发生率）的输入；并从医疗保险费用表和文献中获得了成本输入。我们计算了每避免一次事件的成本，并进行了敏感性分析，以评估结果对输入变化的稳健性。与 SOC 相比，CYP3A5 基因型指导与 SOC 他克莫司剂量相比，肾移植受者避免一次事件的增量成本为 176667 美元，肝移植受者为 364000 美元，心脏移植受者为 12982 美元，肺移植受者为 93333 美元。在肾移植、肝移植、心脏移植和肺移植受者中，CYP3A5 基因型指导他克莫司治疗导致成本节约的可能性分别为 19.8%、32.3%、51.8%和 54.1%。医生使用基因型结果指导临床护理以及具有高 TAC TTR-Rosendaal 的患者比例是驱动 CYP3A5 基因型指导他克莫司治疗成本效益的关键参数。与 SOC 相比，CYP3A5 基因型指导他克莫司治疗在更高的成本下带来了略微更大的获益。需要进一步进行经济评估，以检查中介结果（例如剂量调整），特别是在 CYP3A5 表达者频率较高的人群中。
