NEW YORK (Reuters Health) – New research suggests concerns over the concurrent use of bedaquiline and delamanid in patients with drug-resistant tuberculosis were unwarranted.
“Prior to the study, the World Health Organization recommended that bedaquiline and delamanid, two of the newest drugs to emerge out of the development pipeline for TB, not be used together, because each prolongs the QT interval on the EKG, and the cardiac risk with the two drugs in combination had not been quantified,” Dr. Kelly E. Dooley of Johns Hopkins University School of Medicine, in Baltimore, Maryland, told Reuters Health by email.
To help determine the safety of the combination, Dr. Dooley and colleagues enrolled 84 patients in Peru and South Africa into an open-label trial. The patients had multidrug-resistant or rifampicin-resistant tuberculosis and were receiving multidrug background treatment.
Participants were randomized to treatment with bedaquiline alone, delamanid alone or to the combination. The 31 patients who had HIV also received dolutegravir-based antiretroviral therapy to avert drug interactions with bedaquiline.
Averaged over weeks 8 to 24, the corrected QT interval increased from baseline by a mean of 12.3 ms with bedaquiline, 8.6 ms with delamanid and 20.7 ms with the combination. There were no grade-3 or -4 adverse QTc prolongation events and no deaths during treatment.
As to efficacy, cumulative culture conversion by week 8 was 88% for bedaquiline, 83% for delamanid and 95% for the combination, the researchers report in The Lancet Infectious Diseases. Corresponding proportions at 24 weeks were 92%, 91% and 95%.
“We were very pleased to find that the combined effects of the two drugs on QT was not more than additive, that cardiac safety was acceptable, and that the drugs were well-tolerated when taken together,” said Dr. Dooley. “This, plus other emerging data from observational studies, led to the WHO lifting this restriction, so now the drugs can be used together. This provides an important option for patients with hard-to-treat, drug-resistant TB.”
In an accompanying editorial, Drs. Catherine Hewison and Lorenzo Guglielmetti of Medecins Sans Frontieres, in Paris, note that the study “answers many of the questions surrounding this combination of drugs.”
“In conclusion,” they add, “these results give us the opportunity of re-establishing the correct priorities. Multidrug or rifampicin-resistant tuberculosis is a deadly disease, and patients who need to use both bedaquiline and delamanid should have access to them.”
SOURCE: https://bit.ly/3bupMXO and https://bit.ly/2Nvr1hM The Lancet Infectious Diseases, online February 12, 2021.