Hasan, Tasnim; Medcalf, Ellie; Nyang'wa, Bern-Thomas; Egizi, Erica; Berry, Catherine; Dodd, Matthew; Foraida, Salah; Gegia, Medea; Li, Mengchun; Mirzayev, Fuad; +6 more... Morgan, Hannah; Motta, Ilaria; Nguyen, Linh; Schumacher, Samuel; Schlub, Tim; Fox, Greg; (2023) The Safety and Tolerability of Linezolid in Novel Short-Course Regimens Containing Bedaquiline, Pretomanid, and Linezolid to Treat Rifampicin-Resistant Tuberculosis: An Individual Patient Data Meta-analysis. Clinical infectious diseases, 78 (3). pp. 730-741. ISSN 1058-4838 DOI: https://doi.org/10.1093/cid/ciad653
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Abstract
BACKGROUND: Effectiveness, safety, tolerability, and adherence are critical considerations in shifting to shorter tuberculosis (TB) regimens. Novel 6-month oral regimens that include bedaquiline (B), pretomanid (Pa), and linezolid (L), with or without a fourth drug, have been shown to be as or more effective than the established longer regimens for the treatment of multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB). We aimed to evaluate the safety and tolerability of linezolid in BPaL-containing regimens for the treatment of MDR/RR-TB among recently completed clinical trials. METHODS: A review and meta-analysis was undertaken including published and unpublished data from clinical trials, conducted between 2010 and 2021, that evaluated regimens containing BPaL for the treatment of MDR/RR-TB. Individual patient data were obtained. For each BPaL-containing regimen, we evaluated the frequency and severity of treatment-related adverse events. The risk difference of adverse events for each regimen was calculated, in comparison to patients assigned to receiving the lowest cumulative exposure of linezolid. RESULTS: Data from 3 clinical trials investigating 8 unique BPaL-containing regimens were included, comprising a total of 591 participants. Adverse events were more frequent in groups randomized to a higher cumulative linezolid dose. Among patients who were randomized to a daily dose of 1200 mg linezolid, 68 of 195 (35%) experienced a grade 3-4 adverse event versus 89 of 396 (22%) patients receiving BPaL-containing regimens containing 600 mg linezolid. CONCLUSIONS: Regimens containing BPaL were relatively well tolerated when they included a daily linezolid dose of 600 mg. These novel regimens promise to improve the tolerability of treatment for MDR/RR-TB.
Item Type | Article |
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Faculty and Department | Faculty of Epidemiology and Population Health > Dept of Medical Statistics |
PubMed ID | 37874021 |
Elements ID | 210425 |
Official URL | http://dx.doi.org/10.1093/cid/ciad653 |
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