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

Neil E. Rens*, Carin A. Uyl-De Groot, Jeremy D. Goldhaber-Fiebert, Julio Croda, Jason R. Andrews

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3136-3143
Number of pages8
JournalClinical Infectious Diseases
Volume71
Issue number12
DOIs
Publication statusPublished - 15 Dec 2020

Bibliographical note

Funding Information:This work was supported by the United States Fulbright Program and the Holland Scholarship (to N. R.).
Publisher Copyright:
© 2020 The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

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