Continued success of three-drug, six-month regimen introduces potential first gold standard of XDR-TB care
SEATTLE – With a mortality rate of about 75 percent, tuberculosis that is extensively resistant to first and second-line treatments — XDR-TB — has left physicians with little choice aside from what Dr. Francesca Conradie calls the “kitchen sink” approach. That has meant using as many known effective drugs as a patient can tolerate in hopes of overwhelming bacteria that evolved faster than the medicine meant to wipe them out.
Requiring two years or more of toxic and potentially permanently debilitating treatment, this approach of last resort is so haphazard that when researchers in South Africa launched a trial in 2015 of an experimental regimen for XDR-TB consisting of two recently developed tuberculosis-fighting drugs and one repurposed drug, no “gold standard” of treatment existed with which to compare it.
With interim results of the trial, presented at the Union World Conference on Lung Health in October, that appeared to be changing, with the new regimen representing a reprieve for patients who had run out of options. Of the 51 patients enrolled then in the Nix-TB study 33 had completed treatment, with none showing any evidence of tuberculosis in their sputum after four months. After completing six months of treatment, 20 had been followed for six more months and showed no evidence of illness. Now, Dr. Conradie reported, of 40 patients who have completed the six-month treatment, 31 followed for an additional six months show no signs of tuberculosis.
The Nix TB regimen consists of bedaquiline, which in 2012 became the first new anti-tuberculosis drug in 50 years to receive regulatory approval, pretomanid, an investigational drug developed by TB Alliance, and linezolid, a repurposed drug used normally for other resistant infections. All of the medicines are delivered in pills, in addition to its other benefits simplifying treatment that had included painful injections. The most consistent side effect has been weakness, numbness and tingling in hands and feet from peripheral neuropathy caused by the linezolid, leading 71 percent of patients to have at least one brief treatment interruption due to the drug.
Bringing more validation and no surprises, the results open the way for more evidence and potential improvements. As the trial continues, eventually to enroll 200 patients, the regimen will be tweaked to reduce the amount of linezolid, and potentially, finally introduce a “gold standard” of treatment by which other brief, simpler XDR-TB regimens can be measured.