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Cost-effectiveness of a Pharmacogenomic Test for Stratified Isoniazid Dosing in Treatment of Active Tuberculosis

BACKGROUND: There is marked interindividual variability in metabolism and resulting toxicity and effectiveness of drugs used for tuberculosis treatment. For isoniazid, mutations in the N-acetyltransferase 2 (NAT2) gene explain >88% of pharmacokinetic variability. However, weight-based dosing rema...

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Autores principales: Rens, Neil E, Uyl-de Groot, Carin A, Goldhaber-Fiebert, Jeremy D, Croda, Julio, Andrews, Jason R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819527/
https://www.ncbi.nlm.nih.gov/pubmed/31905381
http://dx.doi.org/10.1093/cid/ciz1212
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author Rens, Neil E
Uyl-de Groot, Carin A
Goldhaber-Fiebert, Jeremy D
Croda, Julio
Andrews, Jason R
author_facet Rens, Neil E
Uyl-de Groot, Carin A
Goldhaber-Fiebert, Jeremy D
Croda, Julio
Andrews, Jason R
author_sort Rens, Neil E
collection PubMed
description BACKGROUND: There is marked interindividual variability in metabolism and resulting toxicity and effectiveness of drugs used for tuberculosis treatment. For isoniazid, mutations in the N-acetyltransferase 2 (NAT2) gene explain >88% of pharmacokinetic variability. However, weight-based dosing remains the norm globally. The potential clinical impact and cost-effectiveness of pharmacogenomic-guided therapy (PGT) are unknown. METHODS: We constructed a decision tree model to project lifetime costs and benefits of isoniazid PGT for drug-susceptible tuberculosis in Brazil, South Africa, and India. PGT was modeled to reduce isoniazid toxicity among slow NAT2 acetylators and reduce treatment failure among rapid acetylators. The genotyping test was assumed to cost the same as the GeneXpert test. The main outcomes were costs (2018 US dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. RESULTS: In Brazil, PGT gained 19 discounted life-years (23 QALYs) and cost $11 064 per 1000 patients, a value of $476 per QALY gained. In South Africa, PGT gained 15 life-years (19 QALYs) and cost $33 182 per 1000 patients, a value of $1780 per QALY gained. In India, PGT gained 20 life-years (24 QALYs) and cost $13 195 per 1000 patients, a value of $546 per QALY gained. One-way sensitivity analyses showed the cost-effectiveness to be robust to all input parameters. Probabilistic sensitivity analyses were below per capita gross domestic product in all 3 countries in 99% of simulations. CONCLUSIONS: Isoniazid PGT improves health outcomes and would be cost-effective in the treatment of drug-susceptible tuberculosis in Brazil, South Africa, and India.
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spelling pubmed-78195272021-01-26 Cost-effectiveness of a Pharmacogenomic Test for Stratified Isoniazid Dosing in Treatment of Active Tuberculosis Rens, Neil E Uyl-de Groot, Carin A Goldhaber-Fiebert, Jeremy D Croda, Julio Andrews, Jason R Clin Infect Dis Major Articles and Commentaries BACKGROUND: There is marked interindividual variability in metabolism and resulting toxicity and effectiveness of drugs used for tuberculosis treatment. For isoniazid, mutations in the N-acetyltransferase 2 (NAT2) gene explain >88% of pharmacokinetic variability. However, weight-based dosing remains the norm globally. The potential clinical impact and cost-effectiveness of pharmacogenomic-guided therapy (PGT) are unknown. METHODS: We constructed a decision tree model to project lifetime costs and benefits of isoniazid PGT for drug-susceptible tuberculosis in Brazil, South Africa, and India. PGT was modeled to reduce isoniazid toxicity among slow NAT2 acetylators and reduce treatment failure among rapid acetylators. The genotyping test was assumed to cost the same as the GeneXpert test. The main outcomes were costs (2018 US dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. RESULTS: In Brazil, PGT gained 19 discounted life-years (23 QALYs) and cost $11 064 per 1000 patients, a value of $476 per QALY gained. In South Africa, PGT gained 15 life-years (19 QALYs) and cost $33 182 per 1000 patients, a value of $1780 per QALY gained. In India, PGT gained 20 life-years (24 QALYs) and cost $13 195 per 1000 patients, a value of $546 per QALY gained. One-way sensitivity analyses showed the cost-effectiveness to be robust to all input parameters. Probabilistic sensitivity analyses were below per capita gross domestic product in all 3 countries in 99% of simulations. CONCLUSIONS: Isoniazid PGT improves health outcomes and would be cost-effective in the treatment of drug-susceptible tuberculosis in Brazil, South Africa, and India. Oxford University Press 2020-01-06 /pmc/articles/PMC7819527/ /pubmed/31905381 http://dx.doi.org/10.1093/cid/ciz1212 Text en © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.
spellingShingle Major Articles and Commentaries
Rens, Neil E
Uyl-de Groot, Carin A
Goldhaber-Fiebert, Jeremy D
Croda, Julio
Andrews, Jason R
Cost-effectiveness of a Pharmacogenomic Test for Stratified Isoniazid Dosing in Treatment of Active Tuberculosis
title Cost-effectiveness of a Pharmacogenomic Test for Stratified Isoniazid Dosing in Treatment of Active Tuberculosis
title_full Cost-effectiveness of a Pharmacogenomic Test for Stratified Isoniazid Dosing in Treatment of Active Tuberculosis
title_fullStr Cost-effectiveness of a Pharmacogenomic Test for Stratified Isoniazid Dosing in Treatment of Active Tuberculosis
title_full_unstemmed Cost-effectiveness of a Pharmacogenomic Test for Stratified Isoniazid Dosing in Treatment of Active Tuberculosis
title_short Cost-effectiveness of a Pharmacogenomic Test for Stratified Isoniazid Dosing in Treatment of Active Tuberculosis
title_sort cost-effectiveness of a pharmacogenomic test for stratified isoniazid dosing in treatment of active tuberculosis
topic Major Articles and Commentaries
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819527/
https://www.ncbi.nlm.nih.gov/pubmed/31905381
http://dx.doi.org/10.1093/cid/ciz1212
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