Skip to main content

Main menu

  • Home
  • Current issue
  • Early View
  • Archive
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • COVID-19 submission information
    • Institutional open access agreements
    • Peer reviewer login
  • Alerts
  • Subscriptions
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

User menu

  • Log in
  • Subscribe
  • Contact Us
  • My Cart

Search

  • Advanced search
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

Login

European Respiratory Society

Advanced Search

  • Home
  • Current issue
  • Early View
  • Archive
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • COVID-19 submission information
    • Institutional open access agreements
    • Peer reviewer login
  • Alerts
  • Subscriptions

Safety of prolonged treatment with bedaquiline in programmatic conditions

Dzmitriy Zhurkin, Elmira Gurbanova, Jonathon R. Campbell, Dick Menzies, Svetlana Setkina, Hennadz Hurevich, Varvara Solodovnikova, Dzmitry Viatushka, Alan Altraja, Alena Skrahina
ERJ Open Research 2022 8: 00685-2021; DOI: 10.1183/23120541.00685-2021
Dzmitriy Zhurkin
1Republican Scientific and Practical Center of Pulmonology and Tuberculosis, Minsk, Belarus
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elmira Gurbanova
2Lung Clinic, University of Tartu, Tartu, Estonia
3WHO Collaborating Centre on TB in Prisons, Baku, Azerbaijan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: elmiragurbanova@gmail.com
Jonathon R. Campbell
4Dept of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Canada
5McGill International TB Centre, Montreal, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jonathon R. Campbell
Dick Menzies
4Dept of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Canada
5McGill International TB Centre, Montreal, Canada
6Montreal Chest Institute, Montreal, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Svetlana Setkina
7Center for Examinations and Tests in Health Service, Minsk, Belarus
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hennadz Hurevich
1Republican Scientific and Practical Center of Pulmonology and Tuberculosis, Minsk, Belarus
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Varvara Solodovnikova
1Republican Scientific and Practical Center of Pulmonology and Tuberculosis, Minsk, Belarus
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dzmitry Viatushka
1Republican Scientific and Practical Center of Pulmonology and Tuberculosis, Minsk, Belarus
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alan Altraja
2Lung Clinic, University of Tartu, Tartu, Estonia
3WHO Collaborating Centre on TB in Prisons, Baku, Azerbaijan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Alan Altraja
Alena Skrahina
1Republican Scientific and Practical Center of Pulmonology and Tuberculosis, Minsk, Belarus
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Figures

  • Tables
  • Supplementary Materials
  • FIGURE 1
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIGURE 1

    Cumulative rates of a) any and b) serious adverse events during treatment, stratified by the duration of bedaquiline (Bdq) exposure.

Tables

  • Figures
  • Supplementary Materials
  • TABLE 1

    Characteristics of patients on standard or prolonged treatment with bedaquiline

    Standard treatment with bedaquilineProlonged treatment with bedaquilineOverallp-value#
    Patients n8330113–
    Patient characteristics
     Median (IQR) age37 (29–47)38 (31–51)38 (30–47)0.74
     Male60 (72.3)21 (70)81 (71.7)0.99
     HIV infection4 (4.8)0 (0)4 (3.5)0.52
     Thyroid disease3 (3.6)0 (0)3 (2.7)0.69
     Alcohol abuse disorder11 (13.3)6 (20)17 (15)0.56
     Diabetes6 (7.2)1 (3.3)7 (6.2)0.75
     Median (IQR) baseline QTcF interval¶388 (360–407)386 (362–416)387 (360–410)0.63
    Microbiological/radiological findings
     AFB smear-positive at baseline+21 (25.3)23 (76.7)44 (38.9)<0.01
     Cavitation on chest radiograph50 (60.2)22 (73.3)72 (63.7)0.29
    Previous treatment
     Never previously treated for TB9 (10.8)1 (3.3)10 (8.8)0.39
     Previously treated with first-line drugs12 (14.5)1 (3.3)13 (11.5)0.19
     Previously treated with second-line drugs62 (74.7)28 (93.3)90 (79.6)0.06
    DST
     DST performed for fluoroquinolones78 (94)30 (100)108 (95.6)0.39
     If DST performed, fluoroquinolone resistant67 (85.9)27 (90)94 (87)0.80
     DST performed for second-line injectables79 (95.2)30 (100)109 (96.5)0.52
     If DST performed, second-line injectable resistant60 (75.9)22 (73.3)82 (75.2)0.97

    Data reported as n (%) unless otherwise specified. HIV: human immunodeficiency virus; AFB: acid-fast bacilli; TB: tuberculosis; DST: drug susceptibility test. #: the following tests were used to calculate p-value: for medians Kruskal–Wallis Test; for proportions Chi square test; for rates Exact Fisher two-sided test. ¶: missing for five patients (two in the bedaquiline 6 months group and three in the bedaquiline >6 months group). +: missing for one patient (one in the bedaquiline 6 months group).

    • TABLE 2

      Regimen received and treatment outcomes among patients on standard and prolonged treatment with bedaquiline

      Bedaquiline <190 daysBedaquiline >190 daysp-value#
      Patients n8330
      Regimen duration
       Median (IQR) total treatment duration, months23.7 (20.7–24.0)24.2 (23.8–24.9)<0.01
       Median (IQR) treatment duration with bedaquiline, months5.5 (5.4–5.6)8.0 (7.3–9.2)<0.01
       Median (IQR) treatment duration with linezolid, months¶23.5 (20.1–24.0)24.1 (23.7–24.4)<0.01
       Median (IQR) treatment duration with injectables, months+5.3 (5.3–21.2)13.8 (10.7–24.2)0.02
      Treatment outcomes
       Number with treatment success77 (92.8)29 (96.7)0.75
       Number with failure1 (1.2)0 (0)1
       Number dying during treatment3 (3.6)1 (3.3)1
       Number lost to follow-up2 (2.4)0 (0)0.96
      Regimen receivedInitialAdded during treatmentInitialAdded during treatment
       Number of drugs in initial regimen, median (IQR)6 (5–6)–6 (6–6)–0.80
       Included moxifloxacin or levofloxacin or gatifloxacin11 (13.3)43 (51.8)0 (0)15 (50)0.08
       Included linezolid83 (100)0 (0)29 (96.7)1 (3.3)0.59
       Included clofazimine80 (96.4)1 (1.2)27 (90)2 (6.7)0.39
       Included terizidone82 (98.8)0 (0)28 (93.3)2 (6.7)0.35
       Included amikacin or capreomycin or kanamycin32 (38.6)6 (7.2)14 (46.7)10 (33.3)0.58
       Included pyrazinamide54 (65.1)2 (2.4)23 (76.7)0 (0)0.35
       Included imipenem/cilastatin with amoxicillin and clavulanic acid42 (50.6)2 (2.4)16 (53.3)7 (23.3)0.97
       Included ethionamide or prothionamide8 (9.6)8 (9.6)2 (6.7)3 (10)0.91

      Data reported as n (%) unless otherwise specified. #: the following tests were used to calculate p-value: for medians Kruskal–Wallis test; for proportions Chi square test; for rates exact Fisher two-sided test. For the regimen received, p-value only refers to initial regimen. ¶: all patients received linezolid during treatment. +: only if received injectables ever during treatment (n=35 bedaquiline 6 months; n=20 bedaquiline >6 months; n=55 overall).

      • TABLE 3

        All adverse events registered during the treatment course among patients on standard and prolonged treatment with bedaquiline

        Bedaquiline <190 daysBedaquiline >190 daysOverallp-value#
        between standard and prolonged
        Number of patients8330113–
        Total treatment duration months1807.8722.72530.5–
        Total treatment with bedaquiline months440.3257.2697.5–
        All adverse events
         Patients experiencing any adverse event81 (97.6)28 (93.3)109 (96.4)–
         Events during treatment total14485852033–
         Incidence per 100 person-months (95% CI)80.1 (76.0–84.3)80.9 (74.5–87.8)80.3 (76.9–83.9)0.83
        Adverse events during periods of treatment
         Events with bedaquiline up to day 190 of treatment7832801063–
          Incidence per 100 person-months (95% CI)177.8 (165.6–190.7)150.1 (133.1–168.8)169.6 (159.5–180.1)0.01
         Events with bedaquiline from day 190 to cessationN/A6262–
          Incidence per 100 person-months (95% CI)N/A87.8 (67.3–112.6)87.8 (67.3–112.6)–
         Events after stopping bedaquiline up to 5 months after bedaquiline cessation288120408–
          Incidence per 100 person-months (95% CI)81.5 (67.5–97.4)72.7 (64.5–81.6)75.1 (68.0–81.6)0.31
         Events >5 months after stopping bedaquiline, to end of treatment377123500–
          Incidence per 100 person-months (95% CI)38.8 (35.0–42.9)38.7 (32.1–46.1)38.8 (35.4–42.3)0.97
         All events during bedaquiline7833421125–
          Incidence per 100 person-months (95% CI)177.8 (165.6–190.7)133.0 (119.2–147.8)161.3 (152.0–171.0)<0.001
         All events up to 5 months after stopping bedaquiline10714621533–
          Incidence per 100 person-months (95% CI)128.0 (1120.5–135.9)114.2 (104.0–125.1)123.5 (117.4–129.9)0.04
        Bedaquiline-related adverse events
         Patients with at least one bedaquiline-related adverse event12315–
         Number of bedaquiline-related adverse events up to 5 months after bedaquiline cessation25429–
          Incidence per 100 person-months (95% CI)3.0 (1.9–4.4)1.0 (0.3–2.5)2.3 (1.6–3.4)0.01
         Category of adverse events–
          QTcF prolongation18 (72)4 (100)22 (75.7)–
          Liver enzyme elevation3 (12)0 (0)3 (10.3)–
          Hyperuricaemia1 (4)0 (0)1 (3.4)–
          Pancreatitis1 (4)0 (0)1 (3.4)–
          Anxiety1 (4)0 (0)1 (3.4)–
          Cardiac failure1 (4)0 (0)1 (3.4)
         Patients stopping treatment due to bedaquiline-related adverse event606–
          Median (IQR) months to bedaquiline cessation5.5 (5.1–5.5)N/A5.5 (5.1–5.5)–

        Data reported as n (%) unless otherwise specified. #: exact Fisher two-sided test was used to calculate p-value.

        • TABLE 4

          Serious adverse events registered during the treatment course among patients on standard and prolonged treatment with bedaquiline

          Bedaquiline <190 daysBedaquiline>190 daysOverallp-value#
          between standard and prolonged
          Number of patients8330113–
          Total treatment duration months1807.8722.72530.5–
          Total treatment with bedaquiline months440.3257.2697.5–
          Total treatment up to 5 months after bedaquiline cessation, months836.5404.41240.9–
          Serious adverse events
           Patients experiencing any serious adverse event32 (38.6)16 (53.3)48 (42.5)–
           Events during treatment total502676–
            Incidence per 100 person-months (95% CI)2.8 (2.1–3.6)3.6 (2.4–5.3)3.0 (2.4–3.8)0.30
          Serious adverse events during periods of treatment
           Events with bedaquiline up to day 190 of treatment371047–
            Incidence per 100 person-months (95% CI)7.5 (5.5–10.0)5.4 (2.6–9.9)8.4 (5.9–11.6)0.07
           Events with bedaquiline from day 190 to cessationN/A00–
            Incidence per 100 person-months (95% CI)N/A0 (0–5.2)0 (0–5.2)–
           Events after stopping bedaquiline up to 5 months after bedaquiline cessation8816–
            Incidence per 100 person-months (95% CI)2.0 (0.9–4.0)5.4 (2.3–10.7)2.9 (1.7–4.8)0.10
           Events > 5 months after stopping bedaquiline, to end of treatment5813–
            Incidence per 100 person-months (95% CI)0.5 (0.2–1.2)2.5 (1.1–5.0)1.0 (0.5–1.7)0.03
           All events up to 5 months after stopping bedaquiline451863–
            Incidence per 100 person-months (95% CI)5.4 (3.9–7.2)4.4 (2.6–7.0)5.1 (3.9–6.5)0.48
          Bedaquiline-related serious adverse events
           Patients with at least one bedaquiline-related serious adverse event516–
           Number of bedaquiline-related serious adverse events up to 5 months after bedaquiline cessation6¶17–
            Incidence per 100 person-months (95% CI)0.7 (0.3–1.6)0.2 (0.1–1.4)0.6 (0.2–1.2)0.22
           Category of serious adverse events–
            QTcF prolongation2 (33.3)1 (100)3 (42.8)–
            Liver enzyme elevation1 (16.7)0 (0)1 (14.3)–
            Pancreatitis1 (16.7)0 (0)1 (14.3)–
            Hyperuricaemia1 (16.7)0 (0)1 (14.3)–
            Cardiac failure1 (16.7)0 (0)1 (14.3)–
           Patients stopping treatment due to bedaquiline-related serious adverse event101–
            Months to bedaquiline cessation1.4N/AN/A–

          Data reported as n (%) unless otherwise specified. #: exact Fisher two-sided test was used to calculate p-value; ¶: patient experienced two serious adverse events: the first was hyperuricaemia 21 days into treatment and the second was aspartate aminotransferase elevation 147 days into treatment.

          • TABLE 5

            Change in mean QTcF interval by month of treatment#

            MonthNumber of patients with measureMean±sd maximum QTcF measureMean±sd change in QTcF from baselineMean±sd change in QTcF from previous monthNumber of patients (%) with QTcF that is >60 ms from baseline
            Baseline108385.7±33.9–––
            1105402.5±33.117.6±24.417.6±24.46 (5.7)
            277414.6±28.726.5±33.910.1±32.412 (15.6)
            394416.1±32.128.5±36.93.2±30.121 (22.3)
            486420.8±33.434.2±37.48.2±33.422 (25.6)
            589422.7±2933.8±38.51.0±33.621 (23.6)
            661426±29.640.2±40.74.2±27.014 (23)
            724418.5±34.634.1±57.4−15±36.88 (33.3)
            812411.2±32.624.8±42.51±24.03 (25)
            910434.1±28.461.9±49.111.7±31.95 (50)
            104442±15.658.8±35.49.5±9.01 (25)

            ECG measures done on the same day were averaged to arrive at an estimate. #: only one patient included in months 11 and beyond.

            • TABLE 6

              Primary and secondary multivariate analyses

              OutcomeEvents/person-monthsEvents/person-monthsMultivariate IRR (95% CI)
              Serious adverse eventsStandard treatment with bedaquiline#Prolonged treatment with bedaquiline
               Up to 5 months after bedaquiline cessation38/76718/4050.82 (0.42–1.61)
               Within the first 190 days of treatment33/41010/1870.73 (0.33–1.61)
              Serious adverse eventsWithin the first 190 days of treatmentFrom day 190 until 5 months after bedaquiline cessation
               Among persons receiving prolonged treatment10/1878/2120.75 (0.30–1.88)

              #: reference group.

              Supplementary Materials

              • Figures
              • Tables
              • Supplementary Material

                Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.

                Supplementary material 00685-2021.SUPPLEMENT

              PreviousNext
              Back to top
              Vol 8 Issue 2 Table of Contents
              ERJ Open Research: 8 (2)
              • Table of Contents
              • Index by author
              Email

              Thank you for your interest in spreading the word on European Respiratory Society .

              NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

              Enter multiple addresses on separate lines or separate them with commas.
              Safety of prolonged treatment with bedaquiline in programmatic conditions
              (Your Name) has sent you a message from European Respiratory Society
              (Your Name) thought you would like to see the European Respiratory Society web site.
              CAPTCHA
              This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
              Print
              Citation Tools
              Safety of prolonged treatment with bedaquiline in programmatic conditions
              Dzmitriy Zhurkin, Elmira Gurbanova, Jonathon R. Campbell, Dick Menzies, Svetlana Setkina, Hennadz Hurevich, Varvara Solodovnikova, Dzmitry Viatushka, Alan Altraja, Alena Skrahina
              ERJ Open Research Apr 2022, 8 (2) 00685-2021; DOI: 10.1183/23120541.00685-2021

              Citation Manager Formats

              • BibTeX
              • Bookends
              • EasyBib
              • EndNote (tagged)
              • EndNote 8 (xml)
              • Medlars
              • Mendeley
              • Papers
              • RefWorks Tagged
              • Ref Manager
              • RIS
              • Zotero
              Share
              Safety of prolonged treatment with bedaquiline in programmatic conditions
              Dzmitriy Zhurkin, Elmira Gurbanova, Jonathon R. Campbell, Dick Menzies, Svetlana Setkina, Hennadz Hurevich, Varvara Solodovnikova, Dzmitry Viatushka, Alan Altraja, Alena Skrahina
              ERJ Open Research Apr 2022, 8 (2) 00685-2021; DOI: 10.1183/23120541.00685-2021
              del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Connotea logo Facebook logo Google logo Mendeley logo
              Full Text (PDF)

              Jump To

              • Article
                • Abstract
                • Abstract
                • Introduction
                • Material and methods
                • Results
                • Discussion
                • Supplementary material
                • Footnotes
                • References
              • Figures & Data
              • Info & Metrics
              • PDF

              Subjects

              • Respiratory infections and tuberculosis
              • Tweet Widget
              • Facebook Like
              • Google Plus One

              More in this TOC Section

              Original research articles

              • Electronically monitored medication adherence in IPF
              • Differential responses of COPD macrophages
              • Specialist assessments in OCS-treated asthma in young adults
              Show more Original research articles

              Tuberculosis

              • Latent tuberculosis screening and treatment in HIV
              • Programme costs of longer/shorter TB regimens and drug import
              Show more Tuberculosis

              Related Articles

              Navigate

              • Home
              • Current issue
              • Archive

              About ERJ Open Research

              • Editorial board
              • Journal information
              • Press
              • Permissions and reprints
              • Advertising

              The European Respiratory Society

              • Society home
              • myERS
              • Privacy policy
              • Accessibility

              ERS publications

              • European Respiratory Journal
              • ERJ Open Research
              • European Respiratory Review
              • Breathe
              • ERS books online
              • ERS Bookshop

              Help

              • Feedback

              For authors

              • Instructions for authors
              • Publication ethics and malpractice
              • Submit a manuscript

              For readers

              • Alerts
              • Subjects
              • RSS

              Subscriptions

              • Accessing the ERS publications

              Contact us

              European Respiratory Society
              442 Glossop Road
              Sheffield S10 2PX
              United Kingdom
              Tel: +44 114 2672860
              Email: journals@ersnet.org

              ISSN

              Online ISSN: 2312-0541

              Copyright © 2022 by the European Respiratory Society