All-Oral Shorter Treatment Regimens for Multidrug- and Rifampicin-Resistant Tuberculosis: Evaluating Their Effectiveness, Safety, and Impact on the Quality of Life of Patients in Lao PDR.

Abstract

Background: Drug-resistant tuberculosis remains a major public health challenge in Lao PDR, with low second-line treatment uptake and suboptimal outcomes. To improve effectiveness, safety, and tolerability, a shorter all-oral regimen for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) was introduced under the TDR Short, all-Oral Regimens for Rifampicin-resistant Tuberculosis (ShORRT) initiative.

Methods: A retrospective and prospective comparative cohort study was conducted across five drug-resistant tuberculosis treatment centres from January 2020 to December 2023. Two programmatic cohorts were analysed during partially overlapping calendar periods: a standard injectable-containing regimen cohort and an all-oral regimen cohort. Outcomes were assessed at the end of treatment and 12 months post-treatment. Safety was evaluated through adverse events, including serious adverse events and adverse events of special interest. Health-related quality of life was measured using EQ-5D-5L and EQ-VAS tools.

Results: Among 126 participants, 65 received the all-oral regimen and 61 the standard regimen. Treatment success was higher in the all-oral group (90.8% vs. 80.3%), with lower mortality (7.5% vs. 16.4%) and fewer serious adverse events (12.3% vs. 19.7%). Anaemia was more common in the all-oral group (46.2%), while hepatotoxicity and QTcF prolongation were more frequent in the standard group. Both groups showed improvements in health-related quality of life, but greater recovery in mobility, daily activities, and anxiety reduction was observed in the all-oral group. Between group differences did not reach statistical significance. No cases of tuberculosis recurrence were reported at 12-month follow-up in either group.

Conclusion: In this programmatic setting, the all-oral, bedaquiline and linezolid-based regimen demonstrated high effectiveness and acceptable safety. Non-significant trends favoured the all-oral regimen for treatment success, mortality, and quality of life, consistent with but not definitive for improved outcomes. These findings support the transition to all-oral regimens as the preferred approach for drug-resistant tuberculosis care, while acknowledging the observational design and limited power.