Comparative Safety and Effectiveness of BPaLM/BPaL, Short-Term, and Long-Term Regimens for Drug-Resistant Tuberculosis: A Multicenter Retrospective Cohort Study

Abstract

Drug-resistant tuberculosis (DR-TB) remains a major global health challenge. Although shorter all-oral regimens have been increasingly adopted, comparative real-world evidence regarding the safety and effectiveness of BPaLM/BPaL, short-term regimen (STR), and long-term regimen (LTR) remains limited. A multicenter retrospective cohort study was conducted among adults with DR-TB treated at three tertiary referral hospitals in South Sulawesi, Indonesia, between January 2021 and December 2025. Treatment effectiveness, adverse drug reactions (ADRs), and severe ADRs were compared across BPaLM/BPaL, STR, and LTR. Multivariable logistic regression identified independent factors associated with treatment effectiveness and severe ADRs. 639 patients were included: 122 received BPaLM/BPaL, 211 STR, and 306 LTR. ADRs occurred in 67.6% and differed across regimens (p<0.001). BPaLM/BPaL had highest ADR frequency (77.0%), while LTR had highest severe ADR proportion (22.4%). Gastrointestinal disorders were frequent (57.6%). Among 561 patients, success was 68.3%, highest with BPaLM/BPaL (87.3%), then LTR (63.9%) and STR (61.6%) (p<0.001). STR, LTR, older age, and comorbidities independently predicted lower effectiveness, whereas ADR predicted higher success. LTR increased severe ADR risk (adjusted OR 2.45; 95% CI 1.17–5.13). BPaLM/BPaL demonstrated the highest treatment effectiveness, whereas LTR was associated with the greatest risk of severe adverse events. Individualized regimen selection and proactive safety monitoring are essential to optimize outcomes in patients with DR-TB.