Characterizing Musculoskeletal and Neurological Toxicities Associated With the BPaLM Regimen: A Clinical Evaluation of Arthralgia and Peripheral Neuropathy in Patients With Multidrug-Resistant Tuberculosis (MDR-TB).

Abstract

Background: Musculoskeletal and neurological toxicities are common side effects of the BPaLM (bedaquiline, pretomanid, linezolid, and moxifloxacin) regimen, an emerging treatment for multidrug-resistant tuberculosis (MDR-TB). These toxicities, particularly arthralgia and peripheral neuropathy, can significantly impair the quality of life of patients undergoing treatment. Despite the promising therapeutic benefits of the BPaLM regimen, the prevalence and severity of these side effects remain underexplored. Understanding these toxicities is crucial to improving patient management strategies and ensuring better treatment adherence.

Objective: This study aims to determine how common and severe musculoskeletal and neurological toxicities, particularly arthralgia and peripheral neuropathy, are among MDR-TB patients treated with the BPaLM regimen.

Materials and methods: This prospective observational study was conducted at the Programmatic Management of Drug-Resistant Tuberculosis in Mardan Medical Complex between January 2024 and April 2025. Patients with MDR-TB undergoing treatment with the BPaLM regimen were monitored for musculoskeletal and neurological toxicities, specifically arthralgia and peripheral neuropathy. Clinical evaluations included assessing the onset, severity, and impact of joint pain and nerve damage, as well as evaluating the effectiveness of pain management and physical therapy interventions. Data collection included demographic information, comorbidities, and baseline physical activity levels. Statistical analysis was performed using SPSS Statistics version 26 (IBM Corp. Released 2019. IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp.), Python (Python Software Foundation, Beaverton, OR, USA), and R 4.4.5 (R Foundation for Statistical Computing, Vienna, Austria) to identify significant predictors of toxicity severity through descriptive statistics, chi-square tests, and decision tree modeling. Kaplan-Meier survival analysis was also conducted to assess the relationship between toxicity severity and treatment outcomes.

Results: Among the 44 MDR-TB patients, 35 (79.54%) experienced mild to moderate arthralgia, with knee pain being most common (34, 77.27%). Peripheral neuropathy was reported in 26 (59.09%) patients, with the lower limbs (20, 45.45%) being most affected. Kaplan-Meier survival analysis revealed a significant difference in survival times based on the severity of arthralgia and peripheral neuropathy, with more severe symptoms correlating with reduced survival duration.

Conclusions: The findings underscore the importance of early identification, regular monitoring, and personalized management strategies to mitigate the burden of these toxicities and enhance patient outcomes.