Effectiveness and safety of delamanid- or bedaquiline-containing regimens among children and adolescents with multidrug resistant or extensively drug resistant tuberculosis: A nationwide study from Belarus, 2015-19

Published: January 14, 2021
Abstract Views: 1917
PDF: 1102
Supplementary: 120
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

There is limited evidence describing the safety and effectiveness of bedaquiline and delamanid containing regimens in children and adolescents with Multidrug-Resistant Tuberculosis (MDR-TB) and Extensively Drug-Resistant Tuberculosis (XDR-TB) globally. In this nationwide descriptive cohort study from Belarus, we examined adverse drug events, time to culture conversion, treatment outcomes including post-treatment recurrence among children and adolescents (<18 years of age) treated with bedaquiline and/or delamanid containing regimens from 2015 to 2019. Of the 40 participants included (55% females; age range 10-17 years), 20 (50%) had XDR-TB and 15 (38%) had resistance to either fluoroquinolone or second-line injectable. Half of the patients received delamanid and another half received bedaquiline with one patient receiving both drugs. AEs were reported in all the patients. A total of 224 AEs were reported, most of which (76%) were mild in nature. Only 10 (5%) AEs were graded severe and one AE was graded life-threatening. A total of 7 AEs (3%) were classified as ‘serious’ and only one patient required permanent discontinuation of the suspected drug (linezolid). Most of the AEs (94%) were resolved before the end of treatment. All patients culture-positive at baseline (n=34) became culture-negative within three months of treatment. Median time to culture conversion was 1.1 months (interquartile range: 0.9-1.6). Two patients were still receiving treatment at the time of analysis. The remaining 38 patients successfully completed treatment. Among those eligible and assessed at 6 (n=32) and 12 months (n=27) post-treatment, no recurrences were detected. In conclusion, treatment of children and adolescents with MDR-TB and XDR-TB using bedaquiline and/or delamanid containing regimens was effective and had favourable safety profile. Achieving such excellent outcomes under programmatic settings is encouraging for other national tuberculosis programmes, which are in the process of introducing or scaling-up the use of these new drugs in their countries.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

WHO. Global tuberculosis report 2019. Geneva: World Health Organization; 2019:1–297. Available from: https://www.who.int/tb/publications/global_report/en/
Dodd PJ, Sismanidis C, Seddon JA. Global burden of drug-resistant tuberculosis in children: a mathematical modelling study. Lancet Infect Dis 2016;16:1193–201.
Jenkins HE, Tolman AW, Yuen CM, et al. Incidence of multidrug-resistant tuberculosis disease in children: systematic review and global estimates. Lancet 2014;383:1572–9.
Jenkins HE, Yuen CM. The burden of multidrug-resistant tuberculosis in children. Int J Tuberc Lung Dis 2018;22:3–6.
García-Basteiro AL, Schaaf HS, Diel R, et al. Adolescents and young adults: a neglected population group for tuberculosis surveillance. Eur Respir J 2018;51.
Skrahina A, Hurevich H, Zalutskaya A, et al. Multidrug-resistant tuberculosis in belarus: the size of the problem and associated risk factors. Bull World Health Organ 2013;91:36–45.
Harausz EP, Garcia-Prats AJ, Seddon JA, et al. New and repurposed drugs for pediatric multidrug-resistant tuberculosis. practice-based recommendations. Am J Respir Crit Care Med 2017;195:1300–10.
WHO. Consolidated guidelines on drug-resistant tuberculosis treatment. Geneva: World Health Organization; 2019:1–104. Accessed on: 2019 Oct 4. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539517/
The Sentinel Project for Pediatric Drug-Resistant Tuberculosis. Management of multidrug-resistant tuberculosis in children: a field guide. Fourth edition. 2018:1–77. Accessed on: 2020 Jul 3. Available from: http://sentinel-project.org/wp-content/uploads/2019/02/Updated_DRTB-Field-Guide-2019-V3.pdf
Migliori GB, Tiberi S, Zumla A, et al. MDR/XDR-TB management of patients and contacts: challenges facing the new decade. The 2020 clinical update by the global tuberculosis network. Int J Infect Dis 2020;92:S15–25.
Esposito S, D’Ambrosio L, Tadolini M, et al. ERS/who tuberculosis consilium assistance with extensively drug-resistant tuberculosis management in a child: case study of compassionate delamanid use. Eur Res J 2014;44:811-5.
Esposito S, Bosis S, Tadolini M, et al. Efficacy, safety, and tolerability of a 24-month treatment regimen including delamanid in a child with extensively drug-resistant tuberculosis: a case report and review of the literature. Medicine (Baltimore) 2016;95:e5347.
Tadolini M, Garcia-Prats AJ, D’Ambrosio L, et al. Compassionate use of new drugs in children and adolescents with multidrug-resistant and extensively drug-resistant tuberculosis: early experiences and challenges. Eur Respir J 2016;48:938–43.
Achar J, Hewison C, Cavalheiro AP, et al. Off-label use of bedaquiline in children and adolescents with multidrug-resistant tuberculosis. Emerg Infect Dis 2017;23:1711-3.
D’Ambrosio L, Centis R, Tiberi S, et al. Delamanid and bedaquiline to treat multidrug-resistant and extensively drug-resistant tuberculosis in children: a systematic review. J Thorac Dis 2017;9:2093-101.
Clinicaltrials.gov. Evaluating newly approved drugs for multidrug-resistant tb (endtb): clinicaltrials.gov identifier: nct02754765. Accessed on: 2020 Jul 2. Available from: https://clinicaltrials.gov/ct2/show/NCT02754765.
Clinicaltrials.gov. Pragmatic clinical trial for a more effective concise and less toxic mdr-tb treatment regimen(s) (tb-practecal): clinicaltrials.gov identifier: nct02589782. Accessed on: 2020 Jul 2. Available from: https://clinicaltrials.gov/ct2/show/NCT02589782.
WHO Regional Office for Europe. Defining tuberculosis the research agenda for the who European region: a study report of the European TB research initiative. Copenhagen, Denmark; 2019:1–23. Accessed on: 2019 Nov 21. Available from: https://apps.who.int/iris/bitstream/handle/10665/327085/9789289054317-eng.pdf?sequence=1&isAllowed=y
US Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. 2017. Accessed on: 2019 Nov 23. Available from: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf.
European Medicines Agency. ICH e2d post-approval safety data management. 2003:1–8. Accessed on: 2020 Jul 31. Available from: https://www.ema.europa.eu/en/ich-e2d-post-approval-safety-data-management.
WHO. Definitions and reporting framework for tuberculosis – 2013 revision. Geneva: World Health Organization; 2013.
Borisov S, Danila E, Maryandyshev A, et al. Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report. Eur Respir J 2019;54:1901522.
WHO Regional Office for Europe, European Centre for Disease Prevention and Control. Tuberculosis surveillance and monitoring in Europe 2020. Copenhagen, Denmark: WHO; 2019:1–164. Accessed on: 2020 Jul 2. Available from: https://www.euro.who.int/en/publications/abstracts/tuberculosis-surveillance-and-monitoring-report-in-europe-2020
WHO Regional Office for Europe. Tuberculosis action plan for the who european region 2016–2020. Copenhagen, Denmark: WHO; 2015. Accessed on: 2019 Nov 21. Available from: http://www.euro.who.int/__data/assets/pdf_file/0007/283804/65wd17e_Rev1_TBActionPlan_150588_withCover.pdf?ua=1
Ajay M.V. Kumar, International Union Against Tuberculosis and Lung Disease, Paris

International Union Against Tuberculosis and Lung Disease, South-East Asia Office, New Delhi; Yenepoya Medical College, Yenepoya (Deemed to be University), Mangaluru, India

How to Cite

Solodovnikova, Varvara, Ajay M.V. Kumar, Hennadz Hurevich, Yuliia Sereda, Vera Auchynka, Dzmitry Katovich, Dzmitry Klimuk, Aliaksandr Skrahin, Svetlana Setkina, Iryna Charnysh, Askar Yedilbayev, and Alena Skrahina. 2021. “Effectiveness and Safety of Delamanid- or Bedaquiline-Containing Regimens Among Children and Adolescents With Multidrug Resistant or Extensively Drug Resistant Tuberculosis: A Nationwide Study from Belarus, 2015-19”. Monaldi Archives for Chest Disease 91 (1). https://doi.org/10.4081/monaldi.2021.1646.