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Tuberculosis
Original research
High-dose rifamycins in the treatment of TB: a systematic review and meta-analysis
  1. Omri A Arbiv1,
  2. JeongMin M Kim1,
  3. Marie Yan1,
  4. Kamila Romanowski1,2,
  5. Jonathon R Campbell3,
  6. Anete Trajman3,4,
  7. Leyla Asadi5,
  8. Federica Fregonese3,
  9. Nicholas Winters6,
  10. Dick Menzies3,6,7,
  11. James C Johnston1,2,3
  1. 1 Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
  2. 2 TB Services, BC Centre for Disease Control, Vancouver, British Columbia, Canada
  3. 3 McGill International TB Centre, McGill University, Montreal, Québec, Canada
  4. 4 Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
  5. 5 Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
  6. 6 Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Québec, Canada
  7. 7 Montreal Chest Institute, McGill University Health Centre, Montreal, Québec, Canada
  1. Correspondence to Dr James C Johnston, Division of TB Control, BCCDC, Vancouver, BC V5Z 4R4, Canada; james.johnston{at}bccdc.ca

Abstract

Background There is growing interest in using high-dose rifamycin (HDR) regimens in TB treatment, but the safety and efficacy of HDR regimens remain uncertain. We performed a systematic review and meta-analysis comparing HDR to standard-dose rifamycin (SDR) regimens.

Methods We searched MEDLINE, Embase, CENTRAL, Cochrane Database of Systematic Reviews and clinicaltrials.gov for prospective studies comparing daily therapy with HDRs to SDRs. Rifamycins included rifampicin, rifapentine and rifabutin. Our primary outcome was the rate of severe adverse events (SAEs), with secondary outcomes of death, all adverse events, SAE by organ and efficacy outcomes of 2-month culture conversion and relapse. This study was prospectively registered in the International Prospective Register of Systematic Reviews (CRD42020142519).

Results We identified 9057 articles and included 13 studies with 6168 participants contributing 7930 person-years (PY) of follow-up (HDR: 3535 participants, 4387 PY; SDR: 2633 participants, 3543 PY). We found no significant difference in the pooled incidence rate ratio (IRR) of SAE between HDR and SDR (IRR 1.00, 95% CI 0.82 to 1.23, I 2=41%). There was no significant difference when analysis was limited to SAE possibly, probably or likely medication-related (IRR 1.07, 95% CI 0.82 to 1.41, I 2=0%); studies with low risk of bias (IRR 0.98, 95% CI 0.79 to 1.20, I 2=44%); or studies using rifampicin (IRR 1.00, 95% CI 0. 0.75–1.32, I 2=38%). No significant differences were noted in pooled outcomes of death, 2-month culture conversion and relapse.

Conclusions HDRs were not associated with a significant difference in SAEs, 2-month culture conversion or death. Further studies are required to identify specific groups who may benefit from HDR.

  • tuberculosis
  • clinical epidemiology

Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. As this is a systematic review and meta-analysis, we only used data from publicly available journal articles. All data used in the manuscript could be reproduced from the original sources.

https://doi.org/10.1136/thoraxjnl-2020-216497

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    Data availability statement

    Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. As this is a systematic review and meta-analysis, we only used data from publicly available journal articles. All data used in the manuscript could be reproduced from the original sources.

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    Footnotes

    • Twitter @JCampbellMcGill

    • Contributors JCJ, RM and JRC initiated the project and were responsible for the design of the protocol. OAA, JMK and MY did the literature review, collected the data and assessed the quality of the studies. OAA analysed the data and wrote the initial draft of the manuscript. OAA, KR, JRC and JCJ interpreted the data. MK, KR, JRC, AT, LA, FF, NW, RM and JCJ were responsible for critical revisions of the manuscript and provided important intellectual content. JCJ was the guarantor and accepts full responsibility for the finished work, conduct of the study, had access to the data and controlled the decision to publish. All authors approved the final version submitted for publication.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.