Effectiveness and cardiovascular safety of delamanid-containing regimens in adults with multidrug-resistant or extensively drug-resistant tuberculosis: A nationwide cohort study from Belarus, 2016-18

Published: January 14, 2021
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To address the sub-optimal treatment outcomes among patients with multidrug-resistant (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), the National TB Programme in Belarus started using new drugs such as bedaquiline and delamanid in 2015-16. In this study, we assessed cardiovascular safety and effectiveness (culture conversion, treatment outcomes and post-treatment recurrence) of delamanid-containing regimens among adults (>18 years) with MDR-TB or XDR-TB from June 2016 to February 2018. This was a nationwide cohort study involving analysis of routinely collected programme data from the national and six regional TB hospitals. Cardiovascular adverse events (AEs) were classified as serious or not, based on international guidelines. We conducted Cox proportional hazards regression and calculated adjusted hazards ratio(aHR) and 95% confidence intervals(CI) to evaluate factors associated with AEs and unsuccessful treatment outcomes (death, failure and lost-to-follow-up). Of 125 patients enrolled (35, 28% females; mean age 43 years), 85(68%) had XDR-TB. All the patients received delamanid and 20 patients received both delamanid and bedaquiline. Cardiovascular AEs (177 episodes in total), were observed in the majority (73%) of patients but were mild and managed easily. The most common cardiovascular AEs were QTcF prolongation (64/177, 36%) and other electrocardiography (ECG) abnormalities (40/177, 23%). There were two instances of serious AEs leading to death, both of which were not related to delamanid. In multivariable analysis, male sex (aHR 0.72; 95% CI 0.51-0.99), and baseline ECG abnormalities (aHR 1.68; 95% CI 1.19-2.36) were associated with cardiovascular AEs. Median time to culture conversion was 1.1 months (interquartile range: 1.0-2.1). Culture conversion was observed in 115 (92%) patients at six months of treatment and 110 (88%) completed the treatment successfully. Loss to follow-up, failure and death were observed in 6%, 4% and 2% patients respectively. Among those assessed at 12 months post-treatment (n=33), recurrence was seen in one patient. The only factor associated with unsuccessful treatment outcomes in multivariable analysis was baseline Hepatitis C co-infection (aHR 3.61; 95% CI 1.09-11.95). In conclusion, treatment using delamanid-containing regimens was effective and had a favourable safety profile. We hope our findings inform the development of national clinical guidelines and scale-up of new drugs in other countries.

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WHO. Global tuberculosis report 2019. Geneva; 2019. Accessed on: 2019 Nov 20. Available from: https://www.who.int/tb/publications/global_report/en/
United Nations. Transforming our world: the 2030 agenda for sustainable development transforming our world: the 2030 agenda for sustainable development. 2016.
Halleux CM, Falzon D, Merle C, et al. The world health organization global aDSM database: generating evidence on the safety of new treatment regimens for drug-resistant tuberculosis. Eur Respir J 2018;51:1701643.
WHO. Consolidated guidelines on drug-resistant tuberculosis treatment. Geneva; 2019 Accessed on: 2019 Nov 20. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539517/
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.
WHO. Position statement on the use of delamanid for multidrug-resistant tuberculosis. Geneva; 2018 Accessed on: 2019 Nov 22. Available from: https://www.who.int/tb/publications/2018/WHOPositionStatementDelamanidUse.pdf?ua=1
von Groote-Bidlingmaier F, Patientia R, Sanchez E, et al. Efficacy and safety of delamanid in combination with an optimised background regimen for treatment of multidrug-resistant tuberculosis: a multicentre, randomised, double-blind, placebo-controlled, parallel group phase 3 trial. Lancet Respir Med 2019;7:249–59.
Pontali E, Centis R, D’Ambrosio L, et al. Recent evidence on delamanid use for rifampicin-resistant tuberculosis. J Thorac Dis 2019;11:S457-60.
Mohr E, Hughes J, Reuter A, et al. Delamanid for rifampicin-resistant tuberculosis: a retrospective study from South Africa. Eur Respir J 2018;51:1800017.
Seung KJ, Khan P, Franke MF, et al. Culture conversion at six months in patients receiving delamanid-containing regimens for the treatment of multidrug-resistant tuberculosis. Clin Infect Dis 2020;71:415-8.
Mok J, Kang H, Koh W-J, et al. Final treatment outcomes of delamanid-containing regimens in patients with MDR-/XDR-TB in South Korea. Eur Resp J 2019;54:1900811.
Olayanju O, Esmail A, Limberis J, et al. A regimen containing bedaquiline and delamanid compared to bedaquiline in patients with drug resistant tuberculosis. Eur Respir J 2020;55:1901181.
Mohr E, Ferlazzo G, Hewison C, et al. Bedaquiline and delamanid in combination for treatment of drug-resistant tuberculosis. Lancet Infect Dis 2019;19:470.
Pontali E, Sotgiu G, Tiberi S, et al. Combined treatment of drug-resistant tuberculosis with bedaquiline and delamanid: a systematic review. Eur Respir J 2018;52:1800934.
Gupta R, Geiter LJ, Hafkin J, et al. Delamanid and QT prolongation in the treatment of multidrug-resistant tuberculosis. Tuberc Lung Dis 2015;19:1261-2.
Ferlazzo G, Mohr E, Laxmeshwar C, et al. Early safety and efficacy of the combination of bedaquiline and delamanid for the treatment of patients with drug-resistant tuberculosis in Armenia, India, and South Africa: a retrospective cohort study. Lancet Infect Dis 2018;18:536–44.
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.
Harausz E, Cox H, Rich M, et al. QTc prolongation and treatment of multidrug-resistant tuberculosis. Int J Tuberc Lung Dis 2015;19:385–91.
Szumowsk JD, Lynch JB. Profile of delamanid for the treatment of multidrug-resistant tuberculosis. Drug Des Devel Ther 2015;9:677–82.
Brigden G, Nhung NV, Skrahina A, et al. Advances in clinical trial design for development of new tb treatments-translating international tuberculosis treatment guidelines into national strategic plans: experiences from Belarus, South Africa, and Vietnam. PLoS Med 2019;16:e1002896.
Ministry of Health of The Republic of Belarus [Internet]. Clinical protocol for diagnosis and treatment of tuberculosis among adults and children. 2019. Accessed on: 2019 Nov 20. Available from: http://www.rnpcpf.by/ru/organizacionno-metodicheskaya-rabota/normativno-pravovye-akty-po-slujbe.html?start=15
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) [Internet]. Medical dictionary for regulatory activities (MEDDRA). 2019. Accessed on: 2019 Nov 23. Available from: https://www.meddra.org/
US Department of Health and Human Services, National Institutes of Health, National Cancer Institute [Internet]. 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. 1998.
Kempker RR, Mikiashvili L, Zhao Y, et al. Clinical outcomes among patients with drug-resistant tuberculosis receiving bedaquiline or delamanid containing regimens. Clin Infect Dis 2019. doi: 10.1093/cid/ciz1107
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

Auchynka, Vera, Ajay M.V. Kumar, Hennadz Hurevich, Yuliia Sereda, Varvara Solodovnikova, Dzmitry Katovich, Svetlana Setkina, Askar Yedilbayev, Aliaksandr Skrahin, and Alena Skrahina. 2021. “Effectiveness and Cardiovascular Safety of Delamanid-Containing Regimens in Adults With Multidrug-Resistant or Extensively Drug-Resistant Tuberculosis: A Nationwide Cohort Study from Belarus, 2016-18 ”. Monaldi Archives for Chest Disease 91 (1). https://doi.org/10.4081/monaldi.2021.1647.

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