Extended follow-up data from a phase 3 clinical trial indicates that bedaquiline-containing drug regimens for rifampicin-resistant tuberculosis (TB) continue to demonstrate superiority compared to a 9-month injectable-based regimen after 132 weeks. The findings, published in The Lancet Respiratory Medicine, reinforce the efficacy and safety of shorter, bedaquiline-based treatments for multidrug-resistant TB.
The STREAM stage 2 trial involved patients aged 15 years and older with rifampicin-resistant TB across seven countries. Participants were randomized to receive one of four treatments: a long regimen (the 20-month regimen recommended by the World Health Organization from 2011 to 2018), a control regimen (a 9-month regimen with the second-line injectable kanamycin), an oral regimen (9 months with bedaquiline replacing kanamycin), or a 6-month regimen (containing bedaquiline and supplemented with 8 weeks of kanamycin).
Initial results at 76 weeks showed the oral and 6-month regimens were more effective than the control regimen, as measured by negative Mycobacterium tuberculosis cultures. The long-regimen arm was terminated early due to inefficacy.
Sustained Efficacy and Safety Profile
The follow-up analysis assessed unfavorable status (death or positive culture) at week 132 in the three remaining groups. The proportion of patients with unfavorable status was 19.6% in the oral regimen arm, 29.3% in the control regimen arm, and 9.8% in the 6-month regimen arm within the modified intention-to-treat population of 517 patients.
Adverse events reported after week 76 were minimal. Treatment-emergent hearing loss was significantly less frequent in the oral regimen group (3%) compared to the control regimen group (8%). There was no significant difference in severe hearing loss between the oral and 6-month regimens.
Reduced Mortality with Bedaquiline Regimens
Mortality rates were notably lower among participants receiving bedaquiline-containing regimens (1.01 per 100 person-years) compared to those on the control regimen (1.52 per 100 person-years).
According to the investigators, "The findings of the STREAM stage 2 trial, combined with results of previous trials, show that shorter bedaquiline-containing regimens are an effective and safe treatment for patients with multidrug-resistant tuberculosis. These data confirm the value of the 9-month regimen recommended in current WHO guidelines and support the use of a 6-month regimen."
