Adverse Events Associated with Treatment of Multidrug-Resistant Tuberculosis in China: An Ambispective Cohort Study

BackgroundMultidrug-resistant tuberculosis (MDR-TB) drugs have never been associated with erythrocytosis. In Eritrea, however, several cases of incident erythrocytosis had been observed in the MDR-TB hospital. This study was aimed at exploring the association between MDR-TB drugs and secondary erythrocytosis, characterising the cases, and identifying other possible risk factors.MethodsA retrospective cohort study was conducted in Merhano National Referral MDR-TB hospital. Data were extracted from physically available clinical cards and laboratory results collected longitudinally between 23 June 2011 and 17 January 2021. Initially, univariate descriptive statistics (frequency, mean (SD), median (IQR) and range) were used as appropriate. Then, χ2 or Fisher χ2 test, and bivariate and/or multivariate Cox proportional hazard model were used to identify the predictors of incident erythrocytosis. All statistical analyses were conducted using R, and a two-sided alpha 0.05 was used to determine the statistical significance.ResultsA total of 257 patients’ medical cards were screened, and 219 were eligible for further analysis. The median age of the patients was 38 years (range: 13–90 years) and 54.8% were males. During the follow-up time, 31 (14.2%) patients developed secondary erythrocytosis yielding an incidence rate of 7.8 cases per 1000 person-months. On average, the median time to onset of the event was found to be 5-months (range: 1–24 months). Males were more likely to develop the event than females (adjusted HR=7.13, 95% CI=1.66 to 30.53), and as body weight increases by 1 kg, the likelihood of developing secondary erythrocytosis was found to increase by 7% (adjusted HR=1.07, 95% CI=1.03 to 1.10). Moreover, all cases of secondary erythrocytosis were found to be possibly associated with the MDR-TB drugs.ConclusionThe authors hypothesised that the incident erythrocytosis is possibly be associated with MDR-TB drugs, and further studies are required to substantiate this finding.

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

PLoS ONE ◽

10.1371/journal.pone.0255357 ◽

2021 ◽

Vol 16 (9) ◽

pp. e0255357

Author(s):

Nguyen Bao Ngoc ◽

Hoa Vu Dinh ◽

Nguyen Thi Thuy ◽

Duong Van Quang ◽

Cao Thi Thu Huyen ◽

...

Keyword(s):

Risk Factors ◽

Adverse Events ◽

Bayesian Model Averaging ◽

Multidrug Resistant ◽

Treatment Regimens ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

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.

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