Bedaquiline for multidrug-resistant tuberculosis and QTc prolongation in California

Shereen Katrak; Phil Lowenthal; Richard Shen; Lisa True; Leslie Henry; Pennan Barry

doi:10.1016/j.jctube.2021.100216

Bedaquiline for multidrug-resistant tuberculosis and QTc prolongation in California

J Clin Tuberc Other Mycobact Dis. 2021 Jan 10:23:100216. doi: 10.1016/j.jctube.2021.100216. eCollection 2021 May.

Authors

Shereen Katrak^{1

2}, Phil Lowenthal¹, Richard Shen³, Lisa True¹, Leslie Henry¹, Pennan Barry^{1

2}

Affiliations

¹ Tuberculosis Control Branch, California Department of Public Health, Richmond, CA, United States.
² Division of Infectious Diseases, University of California, San Francisco, CA, United States.
³ Division of Infectious Diseases, Maine Medical Center, Portland, ME, United States.

Abstract

Background: Bedaquiline (BDQ) is recommended for the treatment of multidrug-resistant tuberculosis (MDR TB), however, it has the potential to prolong QTc interval. We assessed the frequency and severity of QTc prolongation in patients receiving BDQ in California.

Methods: Based on chart review for patients receiving BDQ as part of MDR TB therapy from January 2013-May 2019, we analyzed QTc values at six pre-specified time points during BDQ therapy (baseline, 2, 4, 8, 12, and 24 weeks), as well as peak QTc, time to peak QTc, and the clinical characteristics of patients who had QTc elevation >500 milliseconds (ms) during therapy.

Results: A total of 37 patients were treated with BDQ during the analysis period, with a total of 449 QTc measurements available for analysis. Most patients (89%) received at least one QTc-prolonging drug in addition to BDQ. Median QTc values at all pre-specified time points were <450 ms. Median peak QTc was 455 ms (interquartile range [IQR]: 437-486) and median time to peak was 57 days (IQR: 19-156). Four patients (11%) had a non-transient elevation in QTc to >500 ms, including one patient with profound hypokalemia and one receiving concurrent chemotherapy, but none had cardiac arrhythmia. Less than 10% of patient in our cohort had ECGs performed at all six pre-specified time points.

Discussion: BDQ was generally well-tolerated in a cohort of patients treated for MDR TB in California, with 11% of patients experiencing a non-transient QTc elevation >500 ms, and no episodes of arrhythmia. Frequent ECG monitoring during BDQ therapy presents a challenge for TB clinicians, even in well-resourced countries.

Keywords: Adverse event; Bedaquiline; Multidrug-resistant; Safety; Treatment; Tuberculosis.