Adverse events in bedaquiline- and pretomanid-based regimens for drug-resistant tuberculosis from trial, implementation and pharmacovigilance studies.

The availability of safety data, particularly concerning adverse events (AEs) associated with the new shorter regimen for drug-resistant tuberculosis (TB) containing a bedaquiline-pretomanid-based regimen, is still limited. This systematic review aims to provide a comprehensive and updated analysis of AEs related to this new regimen by combining safety data from clinical trials, implementation and pharmacovigilance studies. We conducted a search using PubMed, Medline and Web of Science to identify studies that reported AE data for bedaquiline-pretomanid-based regimens. In total, 14 studies from various countries were included in the analysis, comprising seven clinical trials, six implementation studies and one pharmacovigilance study. AE detection methods differed between clinical trials and implementation studies. Clinical trials utilised structured and standardised detection methods, whereas implementation and pharmacovigilance studies relied on spontaneous reporting with a higher prevalence of AEs reported in clinical trials (62.2-100%) compared to implementation studies (41.8-72.8%). Serious AEs developed in 2.2-30.2% of patients. Among those with serious AEs, 7.7-54.3% required interruption of TB drugs, while 3.5-13% required withdrawal of TB drugs. AE outcomes showed full recovery in 79.2%. However, 23-32% of patients reported AEs even after completing their treatment. Understanding AEs is crucial for healthcare professionals to enhance patient care, as early detection and appropriate management of AEs is essential in TB treatment to increase tolerability, minimise complications and optimise clinical outcomes. Further research is necessary to implement active monitoring for this new TB regimen in real-world settings.