Frequency of Adverse Events in Patients With Multidrug-Resistant Tuberculosis

Among patients with multidrug-resistant tuberculosis (MDR-TB), adverse events related to treatment with linezolid and injectable drugs were found to be more common compared with those related to bedaquiline and delamanid, according to a multicenter, prospective observational study published in Clinical Infectious Diseases.

Between April 2015 and June 2018, investigators collected data from 16 countries on the incidence and frequency of clinically relevant adverse events among patients with MDR-TB treated with bedaquiline and/or delamanid. Eligible patients included those with either resistance to rifampicin and isoniazid and/or fluoroquinolone plus 1 injectable drug (capreomycin, amikacin, or kanamycin). The median follow-up duration was 16.5 (IQR, 11.5-19.9) months.

A total of 2296 patients were included in the study. At baseline, 71% of patients received bedaquiline, 39.4% received delamanid, and 10.4% received both medications. In addition, 79.5% of patients received linezolid.

The most common clinically relevant adverse events among the included patients were peripheral neuropathy (26.4%), electrolyte depletion (26%), and hearing loss (13.2%). Of note, QT prolongation occurred in 2.7% of patients, and adverse events were most likely to occur among those treated with injectable drugs (n=925) and linezolid (n=1826).

Per 1000 person-months of treatment, the incidence rate (IR) of peripheral neuropathy was 21.5 (95% CI, 19.8-23.2), the IR of electrolyte depletion was 20.7 (95% CI, 19.1-22.4), and the IR of hearing loss was 9.7 (95% CI, 8.6-10.8). Of note, the IR of QT prolongation per 1,000 person-months of treatment was 1.8 (95% CI, 1.4-2.3).

The investigators evaluated clinically relevant adverse events among patients who were exposed to injectable drugs and linezolid. Of patients treated with injectable drugs, 36.8% experienced either hearing loss, acute kidney injury, or electrolyte depletion (IR, 72.8 (95% CI, 66.0-80.0 per 1000 person-months). Peripheral neuropathy, optic neuritis, and/or myelosuppression occurred among 27.8% of patients treated with linezolid (IR, 22.8; 95% CI, 20.9-24.8 per 1000 person-months).

This study was limited by the lack of data on outcomes among patients who experienced adverse events, as well the inability to attribute causality to a single medication due to the overlapping toxicity profiles of many TB medications.

According to the investigators, “given that bedaquiline and linezolid are now both prioritized for the treatment of [patients with] MDR-TB, [these findings] may guide clinicians when constructing [MDR-TB] regimens, monitoring and managing adverse events, and informing patients of what to expect [during their treatment course].”

Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Hewison C, Khan U, Bastard M, et al. Safety of treatment regimens containing bedaquiline and delamanid in the endTB cohort. Clin Infect Dis. Published online January 13, 2022. doi:10.1093/cid/ciac019