Efficacy of isoniazid in paediatric tuberculosis: an individual participant data meta-analysis
Issued Date
2026-01-01
Resource Type
ISSN
09031936
eISSN
13993003
Scopus ID
2-s2.0-105032003265
Pubmed ID
41412716
Journal Title
European Respiratory Journal
Volume
67
Issue
3
Rights Holder(s)
SCOPUS
Bibliographic Citation
European Respiratory Journal Vol.67 No.3 (2026)
Suggested Citation
Béranger A., Solans B.P., Miyakawa R., McIlleron H., Tarning J., Shah I., Aruldhas B.W., Mathew B.S., Kwara A., Peloquin C.A., Mukherjee A., Lodha R., Denti P., Capparelli E.V., Kiser J.J., Bekker A., Chabala C., Choo L., Turkova A., Gafar F., Ruslami R., Nataprawira H.M., Heysell S.K., Thomas T.A., Velpandian T., Day J.N., Bang N.D., Dooley K., Savic R.M. Efficacy of isoniazid in paediatric tuberculosis: an individual participant data meta-analysis. European Respiratory Journal Vol.67 No.3 (2026). doi:10.1183/13993003.01046-2025 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/116945
Title
Efficacy of isoniazid in paediatric tuberculosis: an individual participant data meta-analysis
Author(s)
Béranger A.
Solans B.P.
Miyakawa R.
McIlleron H.
Tarning J.
Shah I.
Aruldhas B.W.
Mathew B.S.
Kwara A.
Peloquin C.A.
Mukherjee A.
Lodha R.
Denti P.
Capparelli E.V.
Kiser J.J.
Bekker A.
Chabala C.
Choo L.
Turkova A.
Gafar F.
Ruslami R.
Nataprawira H.M.
Heysell S.K.
Thomas T.A.
Velpandian T.
Day J.N.
Bang N.D.
Dooley K.
Savic R.M.
Solans B.P.
Miyakawa R.
McIlleron H.
Tarning J.
Shah I.
Aruldhas B.W.
Mathew B.S.
Kwara A.
Peloquin C.A.
Mukherjee A.
Lodha R.
Denti P.
Capparelli E.V.
Kiser J.J.
Bekker A.
Chabala C.
Choo L.
Turkova A.
Gafar F.
Ruslami R.
Nataprawira H.M.
Heysell S.K.
Thomas T.A.
Velpandian T.
Day J.N.
Bang N.D.
Dooley K.
Savic R.M.
Author's Affiliation
University College London
University of California, San Diego
University of California, San Francisco
Université Paris Cité
Rijksuniversiteit Groningen
University of Virginia
University of Cape Town
University of Colorado Anschutz Medical Campus
Vanderbilt University Medical Center
Stellenbosch University
University of Florida College of Medicine
Nuffield Department of Medicine
Universitas Padjadjaran
McGill Faculty of Medicine and Health Sciences
Christian Medical College, Vellore
UF Health
L'Institut de Recherche du Centre Universitaire de Santé McGill
Ministry of Health and Family Welfare
Skaggs School of Pharmacy & Pharmaceutical Sciences
Dr. Rajendra Prasad Centre for Ophthalmic Sciences
Royal Devon and Exeter Hospital
Mahidol Oxford Tropical Medicine Research Unit
University Teaching Hospital Lusaka
University of Zambia School of Medicine
Bai Jerbai Wadia Hospital for Children
Pham Ngoc Thach Hospital
University of California, San Diego
University of California, San Francisco
Université Paris Cité
Rijksuniversiteit Groningen
University of Virginia
University of Cape Town
University of Colorado Anschutz Medical Campus
Vanderbilt University Medical Center
Stellenbosch University
University of Florida College of Medicine
Nuffield Department of Medicine
Universitas Padjadjaran
McGill Faculty of Medicine and Health Sciences
Christian Medical College, Vellore
UF Health
L'Institut de Recherche du Centre Universitaire de Santé McGill
Ministry of Health and Family Welfare
Skaggs School of Pharmacy & Pharmaceutical Sciences
Dr. Rajendra Prasad Centre for Ophthalmic Sciences
Royal Devon and Exeter Hospital
Mahidol Oxford Tropical Medicine Research Unit
University Teaching Hospital Lusaka
University of Zambia School of Medicine
Bai Jerbai Wadia Hospital for Children
Pham Ngoc Thach Hospital
Corresponding Author(s)
Other Contributor(s)
Abstract
Background Isoniazid is a cornerstone of management therapy for tuberculosis (TB). Our aim was to determine the association between isoniazid exposure and clinical outcomes, to develop a pharmacokinetic model, and to optimise the dosing regimen in children treated for drug-susceptible (DS)-TB. Methods For this individual participant data meta-analysis, PubMed was searched for observational studies, involving children (aged 0–18 years), being treated for DS-TB. The relationship between isoniazid exposure and clinical outcomes was analysed using a mixed effects logistic regression model. Pharmacokinetic parameters were described using non-linear mixed effects modelling. The pharmacokinetic target was the median adult area under the concentration–time curve at steady-state (AUC<inf>ss</inf>) of 23.4 mg·h·L<sup>−1</sup>. Results Six studies provided clinical outcomes, including 405 patients, of which 21% had unfavourable outcomes. 16 studies (1255 patients) were included in the pharmacokinetic model. Unfavourable outcomes were only related to lower body mass index (BMI) for age z-score (BAZ) (OR 0.96, 95% CI 0.93–0.99; p<0.05). Isoniazid exposure was impacted by N-acetyltransferase 2 (NAT2) genotype, weight, age and nutritional status (using BAZ). With currently recommended World Health Organization (WHO) doses, isoniazid exposure was similar to that of adults. Pharmacokinetic target attainment was 71.7% and 29.5% for slow and fast metabolisers, respectively (p<0.05); 50.5% for patients with BAZ >0 and 42.6% for malnourished patients (BAZ < −2) (p<0.05). The model-informed dosing regimen showed that fast metabolisers could benefit from higher isoniazid dosing, especially in malnourished children. Conclusion Our findings showed that the only predictor of unfavourable clinical outcomes was a lower BAZ. We support the current WHO-recommended dosing regimen for isoniazid. To equalise and attain our pharmacological target for all children, dosing regimens could be adjusted on NAT2 genotype and nutritional status.