Concomitant treatment with bedaquiline and delamanid (Bdq-Dlm) was determined to be a safe and effective and did not increase the risk for cardiotoxicity in patients with multidrug- and rifampicin-resistant (MDR/RR) tuberculosis (TB) infection, according to results of a study published in Clinical Infectious Diseases.

Researchers assessed the safety and efficacy of concomitant Bdq-Dlm in patients with MDR/RR-TB infection who were also receiving second-line anti-TB medications. This multicenter, prospective, observational cohort study was conducted in 14 countries between April 2015 and September 2018 and included a total of 2731 patients. Patients were followed until the completion of treatment, and severe adverse events and adverse events of special interest (AESI) were monitored and documented. The researchers defined AESI as those that constituted a change in treatment and those that required subsequent electrolytes/thyroxine supplementation.

Among patients included in the study, 472 (17.3%) received concomitant Bdq-Dlm. Of these patients, 89.6% and 84.5% also received linezolid and clofazimine, respectively. Patients who received concomitant Bdq-Dlm had a median age of 36 (IQR, 29-46) years, 61.2% were men, 15.5% had HIV infection, 14.7% had hepatitis C virus infection, 16.1% had diabetes, and 85.5% had previously received second-line anti-TB medications. Fluoroquinolone resistance was observed in 74.2% of patients, and 90.3% had extensive disease, defined as cavitary lung disease shown on chest X-ray, with a positive sputum smear of 3+ at baseline.


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The most commonly reported AESI were peripheral neuropathy and electrolyte depletion in 134 (28.4%) and 94 (19.9%) patients, respectively. Other AESI included acute kidney injury in 40 (8.5%) patients, myelosuppression in 24 (5.1%), and QT prolongation in 7 (1.5%).

Among patients who received concomitant Bdq-Dlm, 358 (78.0%) had favorable outcomes, 33 (7.2%) failed treatment, and 41 (8.9%) died.

This study was limited by the lack of data on preexisting conditions at baseline, thus the risk for adverse events may have been overestimated.

The researchers concluded that the “… wider use of concomitant Bdq-Dlm therapy, increasing clinicians’ awareness about the [decreased] cardiotoxicity risk [associated with Bdq-Dlm], and urging vigilance and increased resources for monitoring other drug-related adverse events will be important next steps in the fight against MDR-TB.” 

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

Reference

Huerga H, Khan U, Bastard M, et. al. Safety and effectiveness outcomes from a 14-country cohort of patients with multi-drug resistant tuberculosis treated concomitantly with bedaquiline, delamanid and other second-line drugs. Clin Infect Diseas. Published online March 4, 2022. doi:10.1093/cid/ciac176