1. Home
  2. Vol 54, No 3 (2022)
  3. Darmayani

Bedaquiline Effect on QT Interval of Drugs-Resistant Tuberculosis Patients: Real World Data

I Gusti Agung Ayu Putu Sri Darmayani, Purwantyastuti Ascobat, Instiaty Instiaty, Yani Jane R Sugiri, Neni Sawitri

Abstract


Background: Bedaquiline (BDQ) is effective as part of treatment regimen for drug-resistant tuberculosis (DR-TB), but the cardiac safety profile of BDQ is not fully elucidated. This study aimed to analyse the cardiac safety of BDQ by examining its effect on the QT interval of DR-TB patients. Methods: This is a retrospective study cohort conducted in two DR-TB referral hospitals in Indonesia. The QT interval before and after therapy using BDQ was measured manually and corrected using the Fridericia formula (QTcF). The QT interval profile was analysed over time during BDQ treatment. Results: A total of 105 subjects participated in the study. The maximum mean difference (standard deviation) of QTcF after treatment with the baseline (∆QTcF) is 34,06 (52,92) ms after three months of therapy. During BDQ treatment, clinically significant QTcF prolongations was observed in 37.1% subjects with neither arrhythmia nor any other adverse cardiac event occurred. The interval QT prolongation led to BDQ discontinuation in 15.2% subjects temporarily and in 6.7% subjects permanently. There were seven deaths (6.7%) during the treatment. Conclusion: During BDQ treatment, maximum QT prolongation was observed after three months of BDQ therapy. Therefore, more intensive cardiac monitoring is recommended during this period and afterwards.


Keywords


bedaquiline; drug-resistant tuberculosis; QT interval prolongation

References


World Health Organization (WHO). WHO Global Tuberculosis Report. World Health Organization; 2021.

Brigden G, Hewison C, Varaine F. New developments in the treatment of drug-resistant tuberculosis: Clinical utility of bedaquiline and delamanid. Infect Drug Resist. 2015;8:367-78.

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;51:1-5.

Cohen K, Maartens G. A safety evaluation of bedaquiline for the treatment of multi-drug resistant tuberculosis. Expert Opin Drug Saf. 2019;18:875-82.

Pontali E, Sotgiu G, Tiberi S, D’Ambrosio L, Centis R, Migliori GB. Cardiac safety of bedaquiline: A systematic and critical analysis of the evidence. Eur Respir J. 2017;50.

EMA. Summary of Product Characteristics of Sirturo (Bedaquiline 100 Mg Tablet); 2014.

International conference on harmonisation (ICH). The clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs (E14). 2005;Version 4 (May).

International conference on harmonisation (ICH). E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non ­ Antiarrhythmic Drugs ­ Questions and Answers (R3). 2017;(June):1-15.

World Health Organization. Companion handbook to the WHO guidelines for the programmatic management of drug-resistant Tuberculosis; 2014.

Kementerian Kesehatan Republik Indonesia. Panduan pelayanan Tuberkulosis resistan obat untuk fasilitas pelayanan kesehatan; 2018.

Pym AS, Diacon AH, Tang SJ, et al. Bedaquiline in the treatment of multidrug- and extensively drug resistant Tuberculosis. Eur Respir J. 2016;47(2):564-74.

Katrak S, Lowenthal P, Shen R, True L, Henry L, Barry P. Bedaquiline for multidrug-resistant tuberculosis and QTc prolongation in California. J Clin Tuberc Other Mycobact Dis. 2021;23:1-6.

Salhotra VS, Sachdeva KS, Kshirsagar N, et al. Effectiveness and safety of bedaquiline under conditional access program for treatment of drug-resistant tuberculosis in India: An interim analysis. Indian J Tuberc. 2020;67:29-37.

Gao JT, Du J, Wu GH, et al. Bedaquiline containing regimens in patients with pulmonary multidrug resistant tuberculosis in China: focus on the safety. Infect Dis Poverty. 2021:1-10

Brust JCM, Gandhi NR, Wasserman S, et al. Effectiveness and cardiac safety of bedaquiline-based therapy for drug-resistant tuberculosis: a prospective cohort study. Infect Dis Soc Am. 2020:1-18.

Isralls S, Baisley K, Ngam E, Grant AD, Millard J. QT interval prolongation in people treated with Bedaquiline for drug-resistant Tuberculosis under programmatic conditions: A retrospective cohort study. Open Forum Infect Dis. 2021;8:1-10.

Guglielmetti L, Tiberi S, Burman M, et al. QT prolongation and cardiac toxicity of new tuberculosis drugs in Europe: A Tuberculosis Network European Trialsgroup (TBnet) study. Eur Respir J. 2018;52:10-3.

Lester RM, Paglialunga S, Johnson IA. QT assessment in early drug development: The long and the short of it. Int J Mol Sci. 2019;20(6).

Kementrian Kesehatan Republik Indonesia. Petunjuk teknis penatalaksanaan Tuberkulosis resistan obat di Indonesia; 2020.

Direktorat Jenderal Pencegahan dan Pengendalian Penyakit Kementerian Kesehatan. Petunjuk Teknis Penatalaksanaan Tuberkulosis Resistan Obat di Indonesia; 2020.

Pontali E, Sotgiu G, Tiberi S, D’Ambrosio L, Centis R, Migliori GB. Cardiac safety of bedaquiline: A systematic and critical analysis of the evidence. Eur Respir J. 2017;50(5).

Harausz E, Cox H, Rich M, Mitnick CD, Zimetbaum P, Furin J. QTc prolongation and treatment of multidrug-resistant tuberculosis. Int J Tuberc Lung Dis. 2015;19:385-91.

Dravniece G, Edwards C, Gebhard A, et al. Guide for QTc monitoring and management of drug-resistant TB patients with QT-prolonging agents. 5th ed. KNCV Tuberculosis Foundation - USAID; 2018.


Full Text: PDF

Refbacks

  • There are currently no refbacks.


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.