Durable three-year outcomes and persistent neuropathy following nine-month all-oral regimens for rifampicin-resistant tuberculosis: a multicentre cohort study in China

Rifampicin-resistant tuberculosis (RR-TB) remains a major public health threat. Nine-month, all-oral regimens containing bedaquiline (Bdq) and linezolid (Lzd) have shown high cure rates, but evidence on the durability of results beyond 24 months and long-term linezolid-induced neurotoxicity is limited. We conducted a multicentre, prospective cohort study (MDR-Chin) involving 124 adults with culture-confirmed MDR/RR-TB or pre-extensively drug-resistant tuberculosis (pre-XDR-TB) enrolled between May 2020 and July 2022. Patients received one of four nine-month, all-oral regimens containing Lzd (600 mg/day). We assessed outcomes 36 months after treatment completion. The primary efficacy outcome was a favourable outcome (absence of failure, relapse, or death). The safety outcome was persistent, clinician-confirmed Lzd-related neuropathic/visual symptoms present for at least 24 months. At 36 months after treatment completion, 111 of 124 participants (89.5%, 95% CI 82.9–93.8) achieved a favourable outcome. No significant differences in favourable outcomes were observed between the four regimens (log-rank p > 0.05). Overall, 28 out of 124 patients (22.6%) reported at least one persistent linezolid-related neuropathic or visual symptom. The most frequent symptom was foot numbness (22/124; 17.7%). In this non-randomised multicentre cohort, nine-month all-oral therapy for RR-TB demonstrated durable three-year outcomes. However, linezolid-related persistent neuropathy remained common and warrants proactive mitigation, including optimisation to reduce cumulative linezolid exposure or adoption of linezolid-sparing alternatives when feasible.