ECONOMIC EVALUATION OF CYP3A5 GENOTYPE-GUIDED TACROLIMUS DOSING IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANT RECIPIENTS: A MONTE CARLO SIMULATION FROM AN INDIAN HEALTHCARE PERSPECTIVE
Author(s)
Betsy Susan Babu, PharmD1, Ganesan Rajalekshmi Saraswathy, PhD2, HARISH KAUSHIK KOTAKONDA, PhD3.
1Department of Pharmacy Practice, M S Ramaiah University Of Applied Sciences, Bengaluru, India, 2Department of Pharmacy Practice, M S Ramaiah University Of Applied Sciences, Bangalore, India, 3Department of DMPK & Clinical Pharmacology, Bugworks Research India Pvt Ltd, BANGALORE, India.
1Department of Pharmacy Practice, M S Ramaiah University Of Applied Sciences, Bengaluru, India, 2Department of Pharmacy Practice, M S Ramaiah University Of Applied Sciences, Bangalore, India, 3Department of DMPK & Clinical Pharmacology, Bugworks Research India Pvt Ltd, BANGALORE, India.
OBJECTIVES: Tacrolimus is the cornerstone of graft-versus-host disease (GVHD) prophylaxis following allogeneic hematopoietic stem cell transplantation (HSCT). However, substantial interindividual pharmacokinetic variability, largely attributed to CYP3A5 polymorphisms, frequently results in delayed therapeutic target attainment, repeated dose modifications, and tacrolimus-related toxicities. Given the high prevalence of CYP3A5 variants in Asian populations, this study evaluated the clinical and economic impact of CYP3A5 genotype-guided Tacrolimus dosing compared with conventional therapeutic drug monitoring (TDM)-based dosing.
METHODS: A decision-tree model and Monte Carlo simulation of 1,000 virtual allogeneic HSCT recipients were developed to compare conventional tacrolimus dosing with CYP3A5 genotype-guided dosing. Clinical inputs were derived from published pharmacogenomic studies, while direct medical costs were obtained from institutional data. To reflect real-world healthcare financing in India, analyses were performed across low-cost (government-funded), medium-cost (corporate insurance-supported care), and high-cost (self-paying/premium care) settings. Outcomes included therapeutic tacrolimus target attainment, acute kidney injury (AKI), acute GVHD, dose modifications, healthcare costs, and incremental cost-effectiveness.
RESULTS: Genotype-guided dosing increased therapeutic tacrolimus target attainment from 16.9% to 47.6%, resulting in 307 additional patients achieving therapeutic concentrations per 1,000 HSCT recipients. Simulated AKI incidence decreased from 24.0% to 17.7% (63 fewer events), while acute GVHD incidence decreased from 29.5% to 22.6% (69 fewer events). Mean healthcare costs per patient were reduced from ₹98,613 to ₹87,531 in low-cost settings, ₹110,703 to ₹97,533 in medium-cost settings, and ₹155,023 to ₹134,629 in high-cost settings, corresponding to savings of ₹11,082, ₹13,170, and ₹20,394 per patient, respectively. Negative ICERs across all scenarios demonstrated economic dominance of genotype-guided dosing.
CONCLUSIONS: CYP3A5 genotype-guided tacrolimus dosing was a dominant strategy, improving therapeutic target attainment, reducing simulated AKI and acute GVHD events, and lowering healthcare costs across diverse healthcare settings. These findings support the adoption of pharmacogenomics-guided tacrolimus therapy into routine allogeneic HSCT care as a clinically beneficial and cost-saving precision medicine approach.
METHODS: A decision-tree model and Monte Carlo simulation of 1,000 virtual allogeneic HSCT recipients were developed to compare conventional tacrolimus dosing with CYP3A5 genotype-guided dosing. Clinical inputs were derived from published pharmacogenomic studies, while direct medical costs were obtained from institutional data. To reflect real-world healthcare financing in India, analyses were performed across low-cost (government-funded), medium-cost (corporate insurance-supported care), and high-cost (self-paying/premium care) settings. Outcomes included therapeutic tacrolimus target attainment, acute kidney injury (AKI), acute GVHD, dose modifications, healthcare costs, and incremental cost-effectiveness.
RESULTS: Genotype-guided dosing increased therapeutic tacrolimus target attainment from 16.9% to 47.6%, resulting in 307 additional patients achieving therapeutic concentrations per 1,000 HSCT recipients. Simulated AKI incidence decreased from 24.0% to 17.7% (63 fewer events), while acute GVHD incidence decreased from 29.5% to 22.6% (69 fewer events). Mean healthcare costs per patient were reduced from ₹98,613 to ₹87,531 in low-cost settings, ₹110,703 to ₹97,533 in medium-cost settings, and ₹155,023 to ₹134,629 in high-cost settings, corresponding to savings of ₹11,082, ₹13,170, and ₹20,394 per patient, respectively. Negative ICERs across all scenarios demonstrated economic dominance of genotype-guided dosing.
CONCLUSIONS: CYP3A5 genotype-guided tacrolimus dosing was a dominant strategy, improving therapeutic target attainment, reducing simulated AKI and acute GVHD events, and lowering healthcare costs across diverse healthcare settings. These findings support the adoption of pharmacogenomics-guided tacrolimus therapy into routine allogeneic HSCT care as a clinically beneficial and cost-saving precision medicine approach.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
EE709
Topic
Clinical Outcomes, Economic Evaluation, Medical Technologies
Disease
Oncology, Personalized & Precision Medicine