Two-month regimen could dramatically cut length of tuberculosis treatment

01 Mar 2023

Results of the TRUNCATE-TB trial show that a strategy of treating patients with an initial two-month, intensive antibiotic regimen, followed by close monitoring and re-treatment if required, was as effective in the long term at treating tuberculosis (TB) as the standard six-month regimen. Shorter treatment may be more appealing to patients and could help ensure they complete their treatment in full.

The findings were published last week in the New England Journal of Medicine and presented at the 2023 Conference on Retroviruses and Opportunistic Infections (CROI).

TB is caused by a bacterial infection of Mycobacterium tuberculosis, which mainly affects the lungs. For more than 40 years, the global standard treatment for TB has been a six-month regimen based around the antibiotic rifampicin (or rifampin). However, the success of treatment is often limited, as sticking to treatment over such a long period of time can be difficult for some people.

In the TRUNCATE-TB clinical trial, researchers wanted to explore whether the standard six-month treatment could be replaced by a strategy of treating patients with an ultra-short regimen, which might require re-treatment for some patients. The primary endpoint was the outcome 96 weeks after starting treatment, irrespective of whether retreatment had been necessary.

The study involved 674 patients with pulmonary TB which was not resistant to rifampicin. Participants were randomised to either: 

  • standard treatment for six months using rifampicin and isoniazid (with pyrazinamide and ethambutol for the first two months) 
  • the TRUNCATE strategy, involving initial treatment with an intensive two-month (eight-week) antibiotic regimen, extended for a further two to four weeks if needed for persistent clinical disease at week eight, monitoring after completion of treatment, with a second course for anyone whose TB was not cured or later returned.

The team tested the strategy using initial treatment with one of four shortened regimens, of which two strategy arms were included in the primary assessment against standard treatment at 96 weeks. These used high doses of either rifampicin and linezolid or bedaquiline and linezolid. Both regimens also included isoniazid, pyrazinamide and ethambutol.

After 96 weeks, researchers observed the number of patients in each group who had either died, had active tuberculosis or were still undergoing treatment. Both the shortened regimens worked well and cured most people with TB, although a few needed additional treatment. It was very rare for the bacteria to become resistant to the drugs used in the trial.

Statistical analyses found that the strategy using two months of initial treatment with bedaquiline and linezolid was noninferior to six months of standard treatment, meaning it did not have significantly worse health outcomes. However, the two-month rifampicin-linezolid strategy was not as successful as standard treatment. The bedaquiline-linezolid group also had the shortest total treatment length with an average of 85 days, compared with 106 days for the rifampicin-linezolid group and 180 days for standard treatment. 

Overall, the TRUNCATE strategy with an initial two-month bedaquiline-linezolid treatment regimen was as effective as standard six-month, rifampicin-based treatment with no additional safety concerns. By shortening the total treatment length, this alternative regimen could improve patients’ motivation to stick to their prescribed treatment and make treatment programmes more efficient.

Future cost-effectiveness analyses will explore whether the added costs of monitoring and retreatment are offset by the costs saved with a shorter treatment duration. 

TRUNCATE-TB took place across south-east Asia and in Uganda and was funded by the Medical Research Council (part of UK Research and Innovation), the Singapore National Medical Research Council, the UK Department for International Development and Wellcome. 

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