Determinants of Adverse Reactions to First-line Antitubercular Medicines: a Prospective Cohort Study

Background: The success of tuberculosis treatment relies on patients adhering to their medication regimen consistently. However, adherence levels tend to decrease among patients who experience adverse drug reactions to antitubercular medications, leading to suboptimal treatment outcomes. Hence, this study aimed to examine the types, incidence rates, and severity of adverse reactions caused by first-line antitubercular drugs. Additionally, it aimed to identify factors associated with the development of these reactions. By doing so, the study aimed to facilitate the provision of personalized and effective treatment to patients, ultimately improving treatment outcomes.

Methods: Newly diagnosed patients with active tuberculosis were monitored from the start of their treatment until the completion of therapy. Any adverse reactions to anti-TB drugs that they encountered were carefully recorded. The collected data were analyzed using appropriate statistical methods such as analysis of variance, Chi-squared test, Fisher's exact test, and independent t-tests. Logistic regression was employed to assess the association between adverse drug reactions and various socio-demographic and clinical factors of the patients, using odds ratios as a measure of association.

Results: Among the 378 patients included in the study, 181 individuals (47.9%) reported experiencing at least one adverse drug reaction, with an incidence rate of 1.75 events per 100-person months. The majority of these reactions occurred during the intensive phase of treatment. The gastrointestinal tract was the most commonly affected system, followed by the nervous system and skin. Patients aged over 45 years (OR = 1.55, 95% CI 1.01-2.39, p = 0.046) and those with extrapulmonary tuberculosis (OR = 2.41, 95% CI 1.03-5.64) were more likely to develop gastrointestinal reactions. Female gender was a significant predictor of both skin (OR = 1.78, 95% CI 1.05-3.02, p = 0.032) and nervous system (OR = 1.65, 95% CI 1.07-2.55, p = 0.024) reactions. Additionally, alcohol use and HIV infection were identified as independent predictors of adverse drug reactions affecting all three systems.

Conclusion: Significant risk factors for developing antitubercular drug adverse reactions include alcohol consumption, cigarette smoking, being HIV positive, female gender and extrapulmonary tuberculosis.