RT Journal Article
SR Electronic
T1 Treatment with Isoniazid or Rifampin for Latent Tuberculosis Infection: Population-Based Study of Hepatotoxicity, Completion, and Costs
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1902048
DO 10.1183/13993003.02048-2019
A1 Lisa A. Ronald
A1 J. Mark FitzGerald
A1 Gillian Bartlett-Esquilant
A1 Kevin Schwartzman
A1 Andrea Benedetti
A1 Jean-François Boivin
A1 Dick Menzies
YR 2020
UL http://erj.ersjournals.com/content/early/2020/01/16/13993003.02048-2019.abstract
AB Background Clinical trials suggest less hepatotoxicity and better adherence with 4 months rifampin (4R) versus 9 months isoniazid (9H) for treating latent tuberculosis infection (LTBI). Our objectives were to compare frequencies of severe hepatic adverse events and treatment completion, and direct health system costs of LTBI regimens 4R and 9H, in the general population of the province of Quebec, Canada, using provincial health administrative data.Methods Our retrospective cohort included all patients starting rifampin or isoniazid regimens between 2003 and 2007. We estimated hepatotoxicity from hospitalisation records, treatment completion from community pharmacy records, and direct costs from billing records and fee schedules. We compared rifampin to isoniazid using logistic (hepatotoxicity), log-binomial (completion), and gamma (costs) regression, with adjustment for age, co-morbidities, and other confounders.Results 10 559 individuals started LTBI treatment (9684 isoniazid; 875 rifampin). Rifampin patients were older with more baseline co-morbidities. Severe hepatotoxicity risk was higher with isoniazid (n=15) than rifampin (n=1), adjusted OR=2.3 (95%CI: 0.3,16.1); there were 2 liver transplants and 1 death with isoniazid and none with rifampin. Overall, patients without co-morbidities had lower hepatotoxicity risk (0.1% versus 1.0%). 4R completion (53.5%) was higher than 9H (36.9%), adjusted RR=1.5 (95%CI:1.3,1.7). Mean costs per patient were lower for rifampin than isoniazid: adjusted Cost Ratio=0.7 (95%CI:0.5,0.9).Conclusion Risk of severe hepatotoxicity and direct costs were lower, and completion was higher, for 4R than 9H, after adjustment for age and co-morbidities. Severe hepatotoxicity resulted in death or liver transplant in three patients receiving 9H, compared to no patients receiving 4R.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Ronald has nothing to disclose.Conflict of interest: Dr. Fitzgerald has nothing to disclose.Conflict of interest: Dr. Bartlett-Esquilant has nothing to disclose.Conflict of interest: Dr. Schwartzman has nothing to disclose.Conflict of interest: Dr. Benedetti has nothing to disclose.Conflict of interest: Dr. Boivin has nothing to disclose.Conflict of interest: Dr. Menzies has nothing to disclose.