Active surveillance for adverse events in patients on longer treatment regimens for multidrug-resistant tuberculosis in Viet Nam

Abstract

Objective Management of multidrug-resistant tuberculosis (MDR-TB) is a significant challenge to the global healthcare system due to the complexity and long duration of the MDR-TB treatment. This study analyzed the safety of patients on longer injectable-based MDR-TB treatment regimens using active pharmacovigilance data. Method We conducted an observational, prospective study based on active pharmacovigilance within the national TB program. A total of 659 MDR-TB patients were enrolled and followed up at 9 TB- hospitals in 9 provinces of all 3 regions in Vietnam between 2014 and 2016. Patients received a treatment regimen (standardized or individualized) based on their drug susceptibility test result and their treatment history. Baseline and follow-up information was collected at the start and during treatment. Adverse events (AE) were defined and classified as serious adverse events (SAEs) or otherwise. Multivariate Cox regression following the Iterative Bayesian Model Averaging algorithm was performed to identify factors associated with AE occurrence. Results Out of 659 patients assessed, 71.3% experienced at least one AE, and 17.5% suffered at least one SAE. The most common AEs were gastrointestinal disorders (38.5%), arthralgia (34.7%), and psychiatric disorders (30.0%). The proportion of patients with nephrotoxicity and hearing loss or vestibular disorders were 7.4% and 15.2%, respectively. 13.1% of patients required modifications or interruption of one or more drugs. In 77.7% of patients, treatment was completed successfully, while 9.3% lost to follow-up, in 3.0% treatment failed, and 7.4% died. Some significant risk factors for nephrotoxicity included diabetes mellitus (HR = 8.46 [1.91–37.42]), renal dysfunction (HR = 8.46 [1.91–37.42]), alcoholism (HR = 13.28 [5.04–34.99]), and a higher average daily dose of injectable drugs (HR = 1.28 [1.14–1.43]). Conclusion While a majority of patients on the longer injectable-based regimens experienced non-serious AEs during MDR-TB treatment, one in six patients experienced at least an SAE. Active TB drug-safety monitoring is useful to understand the safety of MDR-TB treatment and explore the risk factors for toxicity. All-oral, shorter MDR-TB regimens might be able to reduce the inconvenience, discomfort, and toxicity of such regimens and increase adherence and likelihood of successful completion.

Frequency, management and impact of adverse events on treatment outcomes in patients with multidrug resistant tuberculosis in Balochistan, Pakistan

“…Our findings revealed that almost all (99.6%) patients encountered at least one AE, with an average of four different events per patient. The frequency of AEs observed in our study was comparable with the rate reported by a study conducted in India (100%) (Jakasania et al, 2020 ), but was higher than the rates reported by studies conducted at other PMDT units in Pakistan (range: 63.7–72.3%) (Ahmad, Ahuja, et al, 2018 ; Atif et al, 2022 ), China (90.7%) (Zhang et al, 2017 ), KwaZul-Natal (80.6%) (Brust et al, 2013 ), Namibia (89%) (Sagwa et al, 2014 ), Latvia (79%) (Bloss et al, 2010 ) and Viet Nam (71.3%) (Ngoc et al, 2021 ). Variability in the frequency of AEs among published studies can be attributed to several factors.…”

Updates in pulmonary drug‐resistant tuberculosis pharmacotherapy: A focus on BPaL and BPaLM

“…As mentioned previously, adverse events and poor outcomes are more common in the treatment of MDR-TB compared to drugsusceptible TB due to longer drug exposures and the use of less potent or inactive drugs, respectively. [4][5][6][7][8][9][10]49 Serious adverse events, such as hearing loss, vestibular disorders, and visual impairment, often lead to regimen discontinuation and medications adherence issues in patients with drug-resistant TB. 49 One strategy to achieving safe and effective treatment is to shorten the duration of therapy while utilizing novel agents that maintain sterilizing ability.…”

“…[4][5][6][7][8][9][10]49 Serious adverse events, such as hearing loss, vestibular disorders, and visual impairment, often lead to regimen discontinuation and medications adherence issues in patients with drug-resistant TB. 49 One strategy to achieving safe and effective treatment is to shorten the duration of therapy while utilizing novel agents that maintain sterilizing ability.…”

Safety and effectiveness of all-oral and injectable-containing, bedaquiline-based long treatment regimen for pre-XDR tuberculosis in Vietnam

“…Patients were hospitalized during the first 1-2 months, then discharged for ambulatory management at district or commune levels. Adverse events (AEs) were managed and reported monthly following the cohort event monitoring (CEM) protocol as part of a prospective, observational, cohort study of AEs (Bao Ngoc et al, 2021;World Health Organization, 2012).…”

“…Active drug safety Frontiers in Pharmacology frontiersin.org monitoring using the CEM protocol resulted in an early detectionand informed the management of adverse effects that occured during treatment. Our previous study revealed that the risk of SLI related nephrotoxicity was associated with SLI dosing (Bao Ngoc et al, 2021). Therefore, the optimization of the dose of SLI should be considered to minimize the risk of toxicity.…”