(K) Risk of Mortality with Early-Stage Nonadherence to The Regimen in Patients with Drug-Susceptible Tuberculosis: A Nationwide Linkage Database

Publication Number: 301

Background: The clinical importance of adhering to the regimen in tuberculosis (TB) patients has been widely investigated, but most studies were conducted in controlled settings and in limited populations. Moreover, little is known about the evidence of adherence in the intensive phase or early-stage treatment phase, which is at higher risk of transmission, and its impact on mortality.

Objectives: To investigate the level of early-stage nonadherence in the intensive phase, its risk factors, and its association with mortality in patients with drug-susceptible TB.

Methods: We conducted a nationwide cohort study by linking the Korean National Tuberculosis Surveillance System Database and the National Health Information Database. We included all incident patients with incident drug-susceptible TB, who started the recommended regimen by the World Health Organization, between 2013 and 2018. The early-stage adherence during the intensive phase (within 60 days after the start date of the regimen) was measured using the proportion of days covered (PDC). We categorized patients based on levels of adherence as poor (PDC < 50%), moderate (50% to 79%), high (≥80%) adherent groups. We investigated risk factors of early-stage adherence using multinomial logistic regression model. Moreover, to evaluate the association between early-stage adherence and short-term mortality, we estimated hazard ratios (HRs) with 95% CIs using cox proportional hazard model during the continuation phase (within 160 days after the intensive phase).

Results: Among 48,224 eligible patients newly diagnosed with drug-susceptible TB, the overall early-stage adherence level was high in South Korea (Mean PDC: 93.3%; Standard deviation: 0.2%): a) high: 42,882 (88.9%); b) moderate: 3,552 (7.4%); c) poor: 1,790 (3.7%). Early-stage nonadherence was significantly related with older patients, low socioeconomic, and presence of renal failure disease and diabetes. Compared to patients with the high adherent group, poor and moderate adherent group had 89% and 69% higher risk of mortality in continuation phase, respectively [HR: 1.89 (95% CI 1.62-2.22) and HR: 1.68 (1.48-1.90)]. Although the difference in absolute risk of mortality by early-stage nonadherence was small, subgroup analyses showed the risk of mortality was heterogenous according to age group, sex, and economic status.

Conclusions: We found aged population, medical aid beneficial, and patients with renal failure disease and diabetes were less likely to adhere to the regimen in the intensive phase. Early-stage nonadherence was associated with a higher risk of mortality, and the risk was particularly most evident in younger, male, and low-income patients. Based on our findings, healthcare providers should have more attention to these populations.