The standard treatment for drug-susceptible pulmonary tuberculosis has been a 6-month rifampin-based regimen for over four decades. While this treatment has been successful in clinical trials, it has yet to be as effective in national treatment programs due to long-term adherence difficulties and resource constraints. As a result, there is a need for new treatment approaches.
Clinical trials have shown that shorter regimens, ranging from 2 to 4 months, can cure at least 85% of participants, with even higher success rates when fluoroquinolones or rifapentine are included. This suggests that the current 6-month regimen may be unnecessarily long for most patients, leading to overtreatment.
To address this issue, a team of researchers conducted an adaptive, open label, noninferiority trial to test a new treatment strategy. The strategy involved initial treatment with an 8-week regimen of either high-dose rifampin–linezolid or bedaquiline–linezolid (each with isoniazid, pyrazinamide, and ethambutol), extended treatment for persistent clinical disease, follow-up after treatment, and prompt treatment for relapse.
The study published in The New England Journal Of Medicine found that the strategy with an initial bedaquiline-linezolid regimen was non-inferior to standard treatment in terms of clinical outcomes, with a shorter total duration of treatment and no evident safety concerns. However, the strategy with an initial rifampin-linezolid regimen did not meet the noninferiority margin.
The researchers suggest that this new strategy may be more aligned with the desires of patients and more efficient for treatment programs. Further research is needed to refine the strategy, but the study provides hope for more effective and streamlined treatment options for tuberculosis patients.
The TRUNCATE-TB trial has shown that a new tuberculosis treatment strategy involving an initial 8-week regimen containing bedaquiline and linezolid is as effective as standard treatment in reducing the risk of a composite clinical outcome at week 96. The study, which involved clinics in high-burden Asian countries, also found that the new approach resulted in a shorter initial course and a shorter total duration of treatment than the standard treatment.
Participants treated with the new strategy also reported a higher level of motivation to adhere to the initial course. The 13-week reduction in total treatment duration could allow program resources to be redeployed to enhance adherence support during a shorter period, which may help to prevent the decrease in effectiveness seen with standard treatment in programs.
Follow-up after treatment, an essential component of the new strategy, represents an additional burden for people with tuberculosis and treatment programs. However, most participants indicated they would recommend the strategy to others, suggesting a positive overall experience. The strategy was associated with no substantive overall increase in the incidence of adverse events, serious adverse events, or respiratory disability, and there was no evidence that the strategy promoted drug resistance.
The treatment strategy could be refined using alternative drug regimens or monitoring approaches. Any initial regimen with an acceptable side-effect profile and constraints relapse at modest levels may be suitable. The study used bedaquiline with four companion drugs to maximize potency and minimize the risk of resistance. A point-of-care, non-sputum-dependent biomarker of disease activity could support the new strategy.
The study suggests that there may be value in considering a shift in tuberculosis management to a strategy involving initial treatment for the minimum duration needed to cure the majority of people with tuberculosis, extended treatment for persistent clinical disease, and monitoring after treatment to detect relapse in the minority of people who need retreatment.
Future cost-effectiveness analyses are underway to explore whether the additional costs of monitoring after treatment and associated retreatment are offset by the costs saved with reduced treatment duration.