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Predicting tuberculosis relapse in patients treated with the standard 6-month regimen: an individual patient data meta-analysis
  1. Kamila Romanowski1,
  2. Robert F Balshaw2,
  3. Andrea Benedetti3,4,5,
  4. Jonathon R Campbell4,5,
  5. Dick Menzies3,4,5,
  6. Faiz Ahmad Khan3,5,
  7. James C Johnston1,5,6
  1. 1 TB Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
  2. 2 Centre for Healthcare Innovation, University of Manitoba, Winnipeg, Manitoba, Canada
  3. 3 Respiratory Epidemiology and Clinical Research Unit, Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
  4. 4 Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University, Montreal, Quebec, Canada
  5. 5 McGill International TB Centre, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
  6. 6 Division of Respiratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
  1. Correspondence to Dr James C Johnston, British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada; james.johnston{at}


Background Relapse continues to place significant burden on patients and tuberculosis (TB) programmes worldwide. We aimed to determine clinical and microbiological factors associated with relapse in patients treated with the WHO standard 6-month regimen and then evaluate the accuracy of each factor at predicting an outcome of relapse.

Methods A systematic review was performed to identify randomised controlled trials reporting treatment outcomes on patients receiving the standard regimen. Authors were contacted and invited to share patient-level data (IPD). A one-step IPD meta-analysis, using random intercept logistic regression models and receiver operating characteristic curves, was performed to evaluate the predictive performance of variables of interest.

Results Individual patient data were obtained from 3 of the 12 identified studies. Of the 1189 patients with confirmed pulmonary TB who completed therapy, 67 (5.6%) relapsed. In multipredictor analysis, the presence of baseline cavitary disease with positive smear at 2 months was associated with an increased odds of relapse (OR 2.3(95% CI 1.3 to 4.2)) and a relapse risk of 10%. When area under the curve for each multipredictor model was compared, discrimination between low-risk and higher-risk patients was modest and similar to that of the reference model which accounted for age, sex and HIV status.

Conclusion Despite its poor predictive value, our results indicate that the combined presence of cavitary disease and 2-month positive smear status may be the best currently available marker for identifying individuals at an increased risk of relapse, particularly in resource-limited setting. Further investigation is required to assess whether this combined factor can be used to indicate different treatment requirements in clinical practice.

  • tuberculosis
  • clinical epidemiology

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  • Contributors JCJ, FAK and KR initiated the project and were responsible for the design of the protocol. KR was responsible for data management and performed the statistical analysis with advice from RFB and AB. KR, RFB, AB, JRC, DM, FAK and JCJ interpreted the data. KR and JCJ wrote the initial draft of the manuscript. RFB, AB, JRC, DM and FAK were responsible for critical revisions of the manuscript and provided important intellectual content. All authors gave their final approval of the version submitted for publication.

  • Funding JCJ is supported by the Michael Smith Foundation for Health Research. FAK received salary support from the Fonds de Recherche Québec Santé. The researchers were independent of the funders, which had no role in this study.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval University of British Columbia Clinical Ethics Review Board (H16-01282).

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

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