CYTOCHROME P450 3A5 (CYP3A5) GENOTYPE-GUIDED DOSING OF TACROLIMUS IN KIDNEY TRANSPLANTATION IN QATAR: A COST-EFFECTIVENESS ANALYSIS

Objective: To summarize the evidence from the literature on the impact of various genotypes on tacrolimus pharmacokinetic and clinical outcomes in kidney transplant recipients, and to evaluate the cost effectiveness of a genotype guided dosing approach for tacrolimus in kidney transplantation in Qatar. Methods: The thesis constitutes two research phases. Phase one was a systematic review of published meta-analyses (MAs) assessing multiple genotypes that impact tacrolimus therapy outcomes in kidney transplantation. Phase two was an economic simulation-based decision analytic model, constructed from the Hamad Medical Corporation (HMC) perspective, to assess the cost of a genotype-guided dosing therapy approach versus a standard dosing therapy approach against achieving tacrolimus levels within the therapeutic range without adverse drug reactions (ADRs), over six-month follow up, in the kidney transplantation in Qatar. Results: CYP3A5 was most strongly associated with tacrolimus pharmacokinetic and clinical outcomes. Here, the CYP3A5 genotype-guided dosing approach is cost-effective in achieving target tacrolimus levels within the therapeutic range, without ADRs. One-way and multivariate sensitivity analyses confirmed the study outcome robustness. Conclusion: The CYP3A5 genotype-guided dosing of tacrolimus was a cost-effective approach of therapy, over short term follow up, relevant to the standard dosing approach in kidney transplantation in Qatar.