Mycobacterial disease · Treating highly drug-resistant TB
Bedaquiline-Pretomanid-Linezolid Regimens for Drug-Resistant Tuberculosis
| Design | Partially blinded, randomised, dose-ranging trial with four arms |
|---|---|
| Treatment | Bedaquiline and pretomanid with linezolid at 1200 mg or 600 mg, for 26 or 9 weeks |
| Control | Comparison between the four linezolid dosing strategies |
| Population | 181 participants, 88% of whom had extensively drug-resistant or pre-extensively drug-resistant tuberculosis |
| Follow-up | 26 weeks after the end of treatment |
| Primary endpoint | Favourable outcome at 26 weeks after treatment |
| Result | Favourable outcomes occurred in 93%, 89%, 91% and 84% of the 1200 mg/26 week, 1200 mg/9 week, 600 mg/26 week and 600 mg/9 week groups. Peripheral neuropathy occurred in 38%, 24%, 24% and 13%; myelosuppression in 22%, 15%, 2% and 7%; and linezolid dose modification was needed in 51%, 30%, 13% and 13% respectively. |
| Secondary endpoints | Peripheral neuropathy, myelosuppression, optic neuropathy, dose modification |
A total of 84 to 93% of the participants across all four bedaquiline-pretomanid-linezolid treatment groups had a favorable outcome. The overall risk-benefit ratio favored the group that received the three-drug regimen with linezolid at a dose of 600 mg for 26 weeks, with a lower incidence of adverse events reported and fewer linezolid dose modifications.
The trial authors, in the published abstract
A dose-optimisation trial that did exactly what was needed after Nix-TB: kept the efficacy and removed much of the toxicity. 600 mg for 26 weeks is now the standard, and the design is a good model for de-escalating a regimen that works but hurts.
Conradie F, Bagdasaryan TR, Borisov S, et al. Bedaquiline-Pretomanid-Linezolid Regimens for Drug-Resistant Tuberculosis. N Engl J Med 2022 Sep 1;387(9):810-823.