Nix-TB was a single arm prospective study of a regimen of bedaquiline (400 mg daily for 2 weeks followed by 200 mg 3 times a week), pretomanid (200 mg per day) and linezolid (1200 mg per day starting dose, with dose modifications allowed after the first month), given orally for 6 months for Extensively Drug-Resistant (XDR) or treatment intolerant or failed Multidrug-Resistant (MDR) tuberculosis (TB). We report here on long-term efficacy and safety from the recently completed 24-month post-treatment followup in all patients.
We report the study’s secondary endpoint of bacteriologic or clinical failure or relapse at 24 months post-treatment. Peripheral neuropathy associated with linezolid was assessed serially with standard symptoms rated from none (0) to worst (10) with a change from baseline score calculated at end of treatment and 24 months post-treatment. Detailed methods and the primary endpoint at 6 months after completion of therapy have been reported: https://www.nejm.org/doi/full/10.1056/NEJMoa1901814.
At three South African sites 109 participants (65% XDR-TB, 35% MDR-TB; 51% HIV+) were enrolled and comprised the ITT population. 107 were included in the MITT population. All surviving patients, except 1 withdrawal, completed the full course of therapy. At the primary endpoint six months after treatment, as previously reported, there were 98 with favorable outcomes (90% ITT, 92% MITT). After the primary endpoint one patient relapsed 15 months after treatment and one was lost to follow up. Favorable outcomes 24 months post completion of treatment were sustained (88% ITT, 91% MITT) independent of sex or HIV status. A baseline score of 0 in the key neuropathy symptom question ‘pain, aching, burning of feet and legs’ was found in 89 of 107 participants with baseline scores (83%). Of these 89, 83 had scores at an end of treatment visit that occurred at or after month 6, of whom 31 (37%) had positive scores, with 6 (7%) scoring 8-10. Of those 31, 29 had scores at the 24-month-post-treatment-follow-up visit, of whom 6 (21%) had positive scores, with none scoring 8-10.
Results of this simplified, shortened all oral regimen for highly drug resistant TB show sustained high efficacy through 2-year follow-up from end of treatment. Neuropathy from linezolid was common but improved over 24 months of follow-up. A follow-on trial, ZeNix, that investigates the optimal dose and duration of linezolid in the BPaL regimen, has completed enrollment.