Adverse events of tuberculosis preventive therapy among individuals with latent tuberculosis infection: A nationwide cohort study in South Korea

Objectives This study assessed adverse event with tuberculosis preventive therapy (TPT) regimens among individuals with latent tuberculosis infection (LTBI). Methods Using national health insurance data, we analyzed individuals newly diagnosed with LTBI between 2015 and 2020. The TPT group, prescribed 3 months of isoniazid and rifampicin (3HR), 4 months of rifampicin (4R), or 9 months of isoniazid (9H), was matched with a control group through 1:1 propensity score matching. Drug-related adverse events were reported. Results Of 220,483 diagnosed with LTBI, 49.0% received TPT, primarily 3HR (74.6%). The incidence of any adverse events with TPT was 11.90%, with 8.94% of these events being severe events requiring hospitalization. Hepatotoxicity risk was 6.48-, 4.79-, and 3.50-fold with 3HR, 9H, and 4R, respectively, compared to controls. Severe cutaneous adverse reaction risk was 4.27-, 1.83-, and 1.93-fold with 3HR, 9H, and 4R. 4R had the lowest risk of any adverse events, while 3HR had the highest. Permanent discontinuation occurred in 2.3%, 3.1%, and 3.3% with 4R, 9H, and 3HR, respectively. Unlike 9H, rifampicin-based regimens showed no age-related trend in adverse event risk. Conclusions 4R is a better option considering safety across a broad age range, suggesting it could be encouraged in the LTBI population.