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.