{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:44:39Z","timestamp":1791582279999,"version":"4.3.4"},"reference-count":53,"publisher":"European Respiratory Society (ERS)","issue":"3","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publications.ersnet.org\/user-licence"}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2025,10,18]]},"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      For this individual participant data meta-analysis, PubMed was searched for observational studies, involving children (aged 0\u201318\u2005years), 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\u2013time curve at steady-state (AUC\n                      <jats:sub>ss<\/jats:sub>\n                      ) of 23.4\u2005mg\u00b7h\u00b7L\n                      <jats:sup>\u22121<\/jats:sup>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\u20130.99; p&lt;0.05). Isoniazid exposure was impacted by\n                      <jats:italic>N<\/jats:italic>\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&lt;0.05); 50.5% for patients with BAZ &gt;0 and 42.6% for malnourished patients (BAZ &lt;\u2009\u22122) (p&lt;0.05). The model-informed dosing regimen showed that fast metabolisers could benefit from higher isoniazid dosing, especially in malnourished children.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1183\/13993003.01046-2025","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T14:15:13Z","timestamp":1766067313000},"page":"2501046","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Efficacy of isoniazid in paediatric tuberculosis: an individual participant data meta-analysis"],"prefix":"10.1183","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9751-8249","authenticated-orcid":false,"given":"Agathe","family":"B\u00e9ranger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bel\u00e9n 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