ASSOCIATION OF EARLY ADVERSE DRUG REACTION SIGNALS AND PREMORBID LIVER FUNCTION WITH TREATMENT DISCONTINUATION IN YOUNG MEN WITH TUBERCULOSIS: A RETROSPECTIVE COHORT STUDY USING LINKED NATIONWIDE DATABASES
Author(s)
Aerang Hyeon, BSN1, Hae Sun Suh, MA, MS, PhD2.
1Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul, Korea, Republic of, 2College of Pharmacy, Kyung Hee University, Seoul, Korea, Republic of.
1Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul, Korea, Republic of, 2College of Pharmacy, Kyung Hee University, Seoul, Korea, Republic of.
OBJECTIVES: To examine whether early adverse drug reaction (ADR) signals and premorbid liver function are associated with treatment discontinuation during the first 180 days of active tuberculosis treatment in young men.
METHODS: A retrospective cohort study used four linked Korean nationwide databases: military conscription examination, tuberculosis notification, health insurance claims, and eligibility (2015-2024). Men newly initiating first-line anti-tuberculosis drugs (no anti-tuberculosis prescription in the prior 365 days) and linkable to a premorbid conscription examination preceding the index year were included. Baseline exposures were any early ADR signal (hepatotoxic, cutaneous, or gastrointestinal events identified early in treatment from diagnosis codes) and premorbid liver elevation (AST or ALT >40 IU/L). The primary outcome was treatment discontinuation through day 180, defined as the first prescription gap exceeding 15 days (time-to-event, censored at day 180). Multivariable Cox proportional hazards regression estimated crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), adjusting for BMI, diabetes and chronic liver disease.
RESULTS: Of 1,953 men (mean age 22.7 years; all male), 676 had an early ADR signal and 1,277 did not. Treatment discontinuation through day 180 occurred in 188 men overall, with 68 (10.1%) of those with a signal versus 120 (9.4%) of those without. Any early ADR signal was not significantly associated with discontinuation (crude HR 1.00, 95% CI 0.74-1.34; adjusted HR 1.01, 95% CI 0.75-1.36). Premorbid liver elevation (88 men) was similarly non-significant (crude HR 0.92, 95% CI 0.45-1.86; adjusted HR 1.00, 95% CI 0.48-2.09).
CONCLUSIONS: In this nationwide linked cohort, early ADR signals and premorbid liver function were not significantly associated with treatment discontinuation during active tuberculosis treatment. Early safety signals alone may be insufficient to identify discontinuation risk, which may instead relate to broader patient and treatment factors.
METHODS: A retrospective cohort study used four linked Korean nationwide databases: military conscription examination, tuberculosis notification, health insurance claims, and eligibility (2015-2024). Men newly initiating first-line anti-tuberculosis drugs (no anti-tuberculosis prescription in the prior 365 days) and linkable to a premorbid conscription examination preceding the index year were included. Baseline exposures were any early ADR signal (hepatotoxic, cutaneous, or gastrointestinal events identified early in treatment from diagnosis codes) and premorbid liver elevation (AST or ALT >40 IU/L). The primary outcome was treatment discontinuation through day 180, defined as the first prescription gap exceeding 15 days (time-to-event, censored at day 180). Multivariable Cox proportional hazards regression estimated crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), adjusting for BMI, diabetes and chronic liver disease.
RESULTS: Of 1,953 men (mean age 22.7 years; all male), 676 had an early ADR signal and 1,277 did not. Treatment discontinuation through day 180 occurred in 188 men overall, with 68 (10.1%) of those with a signal versus 120 (9.4%) of those without. Any early ADR signal was not significantly associated with discontinuation (crude HR 1.00, 95% CI 0.74-1.34; adjusted HR 1.01, 95% CI 0.75-1.36). Premorbid liver elevation (88 men) was similarly non-significant (crude HR 0.92, 95% CI 0.45-1.86; adjusted HR 1.00, 95% CI 0.48-2.09).
CONCLUSIONS: In this nationwide linked cohort, early ADR signals and premorbid liver function were not significantly associated with treatment discontinuation during active tuberculosis treatment. Early safety signals alone may be insufficient to identify discontinuation risk, which may instead relate to broader patient and treatment factors.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
EPH66
Topic
Epidemiology & Public Health, Real World Data & Information Systems
Topic Subcategory
Safety & Pharmacoepidemiology
Disease
Infectious Disease (non-vaccine)