Aim: 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 six-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, 31.0% (54) missed doses due to ADRs. 4,217/31,320 (13.5%) of doses were missed- 20.9% (880/4,217) were due to ADRs. 18/174 (10.3%) patients discontinued treatment early, 2/18 (11.1%) 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 one day in length versus only 9.1% (7/77) for ADR-related ones. Hepatobiliary disorders were the leading ADR group causing missed doses. Metabolism and nutrition and hepatobiliary ADRs caused the longest median durations of missed doses. 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 minimise missed doses, reducing unfavourable outcomes.

Introduction: A key reason for the failure of anti-tuberculosis (TB) treatment is missed doses (instances where medication is not taken). Adverse drug reactions (ADRs) are one cause of missed doses, but the global evidence for this, their relative contribution to missed doses versus other causes, the patterns of missed doses due to ADRs, and the specific ADRs associated with missed doses have not been appraised. We sought to address these questions through a scoping review. Methods: MEDLINE, Embase and Web of Science were searched on 3 November 2021 using terms around active TB, missed doses and treatment challenges. Studies reporting both ADR and missed dose data were examined. (PROSPERO: CRD42022295209). Results: Searches identified 108 eligible studies. 88/108 (81%) studies associated ADRs with an increase in missed doses. 33/61 (54%) studies documenting the reasons for missed doses gave ADRs as a primary reason. No studies examined patterns of missed doses due to ADRs. 41/108 (38%) studies examined associations between 68 types of ADR (across 15 organ systems) and missed doses. Nuance around ADR-missed doses relations regarding drug susceptibility testing profile and missed dose originator was found. Conclusions: There is extensive evidence that ADRs are a key driver for missed doses of anti-TB treatment. Some papers examined specific ADRs, none evaluated the patterns of missed doses due to ADRs, demonstrating a knowledge deficit. Knowing why doses both are and are not missed due to ADRs is essential in providing targeted interventions to improve treatment outcomes.