A short-course strategy for the treatment of tuberculosis that lasts just 8 weeks appears to be both safe and effective, researchers say.
The strategy involves initial intensive treatment with an 8-week bedaquiline-linezolid regimen, which was found to be non-inferior to standard 6-month therapy, according to findings of an international trial published in the New England Journal of Medicine.
The trial enrolled 675 patients with confirmed rifampin-susceptible pulmonary tuberculosis at 18 sites in five countries, of whom only 4 (0.6%) were lost to follow up.
Participants randomised to the control group received standard tuberculosis treatment for 24 weeks, consisting of 8 weeks of isoniazid, rifampin, ethambutol, and pyrazinamide, followed by 16 weeks of isoniazid and rifampin.
Two other treatment arms received isoniazid, pyrazinamide, and ethambutol alongside either high-dose rifampin plus linezolid or bedaquiline plus linezolid for 8 weeks, after which point patients were evaluated for persistent disease and further treatment.
Data showed that only the treatment strategy based on bedaquiline-linezolid was non inferior to standard treatment with regard to the primary outcome – a composite of death, ongoing treatment or active disease at week 96.
A primary outcome event was recorded for 4% in the control group, compared to 11% in the rifampin-linezolid group and 6% in the bedaquiline-linezolid group.
The majority of patients (86%) taking the bedaquiline-linezolid regimen did not require therapy after 8 weeks, and the mean total length of treatment (85 days) was also under half of that in the control arm (180 days).
The researchers said there were “no evident safety concerns”, with no significant differences in the incidences of grade 3 or 4 adverse events, serious adverse events, and death between the treatment groups.
“In the TRUNCATE-TB trial, the toxic effects appeared to be quite limited. In fact, this is one of many trials that suggest that the original concerns about bedaquiline might be overstated, at least for patients who undergo prescreening with electrocardiography,” noted Drs Eric Rubin and Véronique Dartois in a linked editorial.
As to whether the findings will fuel any significant change in clinical practice, the editorialists commented that while a two month treatment duration of treatment “might not be revolutionary” it could be “very helpful”, given the logistical and clinical challenges of administering and tracking treatment for 24 weeks.
Points to consider
However, there are obstacles to consider, they stressed, including the very high rate of treatment adherence observed in the trial, which they believe to be much higher that what would likely occur in clinical practice. Lower adherence could equate to higher treatment failure at 2 months, they wrote.
Also, the treatment strategy essentially cherry picked patients for extended courses of therapy following careful assessment. “Although this approach is possible within the confines of a trial, it could require considerable resources that are not now available in many tuberculosis control programs,” they noted.
However, while implementing this treatment algorithm might pose challenges, “any added burden might be offset by reduced costs, better adherence, and increased patient satisfaction,” they concluded.