Safety of treatment regimens for drug-resistant TB over a 15-year period: a scoping review

BACKGROUND: A previous review summarised the evolution and efficacy of the regimens to treat rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB), underscoring the persistent need for efficacious shorter treatments. The aim of this scoping review was to explore safety, quality of life (QoL), and unmet needs associated with RR/MDR-TB in studies published between 2009 and 2024. METHODS: We searched PubMed/MEDLINE, Embase, Cochrane CENTRAL, Scopus, and Web of Science for studies reporting safety, QoL, and unmet needs in the last 15 years. RESULTS: Fifty-seven studies including 9,874 patients were identified, with significant variation in geographic distribution, sample size, and other core variables. The overall proportion of serious adverse events (AEs) ranged between 0.2% and 10.1% in retrospective studies, 1.0%-72.4% in prospective cohorts, and 20.0%-25.0% in experimental studies, with no data on QoL. Almost all studies containing linezolid (LZD) reported gastrointestinal and haematological AEs. In studies based on individual patient data, AEs associated with bedaquiline (1.7%-2.4%) and fluoroquinolones (3%-4%) were less frequent than those associated with LZD (14.1%-17.2%). The World Health Organization 95% credible interval range was 10.1%-27.0%. CONCLUSION: While efficacious RR/MDR-TB regimens are recommended, individual drugs still cause AEs potentially leading to decreased adherence. New efficacious treatments with improved safety/tolerability profiles are needed.