Adverse drug reactions, particularly liver disorders, drive interruptions in anti-tuberculosis treatment: A retrospective cohort study

Aims: Adverse drug reactions (ADRs) are a key driver of missed doses of anti-tuberculosis (TB) therapy. We aimed to determine the relative burden of ADR-driven missed doses, the missed dose patterns associated with ADRs, and the association between specific ADRs and missed doses. Methods: In this retrospective cohort study, adults (≥18 years) who began the standard 6-month drug-sensitive anti-TB regimen in an outpatient facility in Riga, Latvia (May 2015–September 2022) and missed at least one dose of treatment were included. Data were collected from medical records and observed therapy records. Missed doses were subdivided into early discontinuation or sporadically missed. Descriptive analyses and lasagne plots were used. Results: Across 174 patients, 54 (31.0%, CI: 24.2–37.9%) missed doses due to ADRs. Of 31 320 doses, 4217 (13.5%, CI: 13.1–13.9%) were missed, 20.9% (880/4217, CI: 19.6–22.1%) were due to ADRs. Eighteen (10.3%) of the 174 patients discontinued treatment early, two of which (11.1%) were due to ADRs. Doses missed due to ADRs caused longer yet less frequent periods of sporadic missed doses: 56.4% (479/849) of sporadic missed doses were 1 day in length vs. only 9.1% (7/77) for ADR-related ones. Hepatobiliary disorders were the leading ADR group causing missed doses. Hepatobiliary ADRs caused long median durations of missed doses (median 15.0, CI: 13.0–22.0). Conclusion: Our study underscores the importance of ADRs as a cause of missed doses of treatment, particularly hepatobiliary disorders. Regimens that are less prone to ADRs and strong healthcare system support structures for patients with ADRs are required to minimize missed doses, reducing unfavourable outcomes.