Cost-effectiveness analysis of genotype screening and therapeutic drug monitoring in patients with inflammatory bowel disease treated with azathioprine therapy: a Chinese healthcare perspective using real-world data


Abstract

Background: This study aimed to analyze the cost-effectiveness of combining screening for thiopurine methyl transferase (TPMT) and nucleotide triphosphate diphosphatase (NUDT15) defective alleles with therapeutic drug monitoring (TDM) in Chinese patients with inflammatory bowel disease (IBD) treated with azathioprine (AZA).

Methods: We evaluated the cost-effectiveness of combining screening for NUDT15 and TPMT deficiency with TDM in patients receiving AZA treatment over a 1-year horizon by developing a decision tree model. Real-world data and published literature were used to derive model inputs. The model''s primary outcomes included quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). One-way and probabilistic sensitivity analyses were used to address uncertainty.

Results: Compared to NUDT15 genotyping, the combined TPMT/NUDT15 genotyping strategy cost an additional $13.83, yielding an ICER of $3,929.54/QALY, which was under the willingness-to-pay level of $30,425 per QALY in China. Compared to strategies with singular TPMT genotyping or no genotyping, the combined TPMT/NUDT15 genotyping strategy gained 0.00406 and 0.00782 QALYs and reduced the cost by $25.15 and $99.06, respectively. Additionally, incorporating TDM of AZA was more effective and less expensive than strategies without TDM. One-way sensitivity analysis revealed the expense attached to severe myelotoxicity to be the factor with the greatest influence in the present research. The application of the combined genotype screening strategy with TDM of AZA treatment was found to have a 91.7% chance of being cost-effective.

Conclusions: For Chinese patients with IBD who receive an AZA regimen, a strategy involving combined NUDT15/TPMT genotype screening prior to treatment initiation and incorporating TDM for treatment management is cost-effective compared to strategies involving genotyping of NUDT15 or TPMT alone or genotyping without TDM.

Keywords: Genotype screening; azathioprine (AZA); cost-effectiveness; inflammatory bowel disease (IBD); therapeutic drug monitoring (TDM).

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-1980). Prof. PH reports that this study was supported by the Social Development Guiding (Key) Project of Fujian Provincial Science and Technology Department, 2020Y0027. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Decision tree of the baseline case. Circles represent chance nodes and squares represent a decision node.
Figure 2
Figure 2
Results of one-way sensitivity analysis of combined TPMT/NUDT15 genotyping versus NUDT15 genotyping. The diagram compares the incremental cost-effectiveness ratios (ICERs) of combined TPMT/NUDT15 genotyping and NUDT15 genotyping for different model input parameters. The model’s robustness was tested by performing one-way sensitivity analysis by varying key parameters over plausible ranges to assess their global effect on the ICER. The longer the bar, the greater the sensitivity of the global results to variations in that key parameter. The orange bar represents the ICER at the minimum parameter value, and the gray bar represents the ICER at the maximum parameter value. ICER, incremental cost-effectiveness ratio; QALYs, quality-adjusted life-years; TPMT, thiopurine methyl transferase; NUDT15, nucleotide triphosphate diphosphatase; TDM, therapeutic drug monitoring.
Figure 3
Figure 3
Cost-effectiveness acceptability curves. Probabilistic sensitivity analyses results on the basis of 10,000 Monte Carlo simulations, which includes the sampling of model variable values from distributions imposed on variables to indicate uncertainty regarding the cost-effectiveness of combined genotyping at various willingness-to-pay thresholds. The combined genotyping strategy has a 91.7% chance of being cost-effective at a threshold of $30,425 per QALY in China. TPMT, thiopurine methyl transferase; NUDT15, nucleotide triphosphate diphosphatase; QALYs, quality-adjusted life-years.
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