Fluticasone/salmeterol treatment for chronic obstructive pulmonary disease (COPD) may be associated with a higher risk of active tuberculosis (TB), according to a study published in BMC Infectious Diseases.
Inhaled corticosteroids (ICS) in combination with long-acting β2-agonists (LABAs) are used for treatment of COPD; the most common combinations are budesonide/formoterol and fluticasone/salmeterol. Previous studies have highlighted safety differences between these 2 treatment combinations and suggested that budesonide/formoterol is associated with higher risks of pneumonia, sepsis, and death than fluticasone/salmeterol. Recent evidence suggested that systemic and ICS use may increase a patient’s risk of TB; however, no comparison on TB risk between these 2 treatment combinations has been performed. This study investigated the incidence of active TB among COPD patients in patients using fluticasone/salmeterol vs budesonide/formoterol and identified differences between these 2 groups.
Using a subset of the Taiwan National Health Insurance Research Database, adult patients at least 40 years of age who received treatment with fluticasone/salmeterol or budesonide/formoterol for more than 90 days were identified and included. Patients were followed until December 2011, the end of fixed combination treatment, emigration or death, whichever came first. A budesonide/formoterol group (n=7436) was matched 1:1 to a larger fluticasone/salmeterol group (n=11,515). The outcome of this study was incidence of active TB. A pairwise 1:1 propensity score matching was used to prevent potential confounding from unbalanced covariates.
The fluticasone/salmeterol group saw significantly higher rates of active TB compared to the budesonide/formoterol group (adjusted hazard ratio [aHR], 1.41; 95% CI, 1.17-1.70); the incidence rate of active TB was 0.94% and 0.61%, respectively. The same trend was observed after propensity score matching (aHR, 1.45; 95% CI, 1.14-1.85) and after a competing risk analysis (HR, 1.44; 95% CI, 1.19-1.75). Furthermore, a higher incidence of TB was observed in the fluticasone/salmeterol group when compared to the budesonide/formoterol group across all subgroups; significantly higher incidences were observed in the following subgroups: patients who were men, patients without diabetes mellitus, patients without cancer, and patients without autoimmune disease (all P <.05).
The dose and duration of LABA/ICS was not assessed in the study. Some other limitations include lack of confounders (eg, BMI, pulmonary function, smoking status, and history of latent TB) and lack of microbiological data that were not available in the database.
“In contrast to previous meta-analyses which showed that ICS increased the risk of tuberculosis, this study is the first one to point out patients using fluticasone/salmeterol are at a higher risk of tuberculosis than patients using budesonide/formoterol,” concluded the study authors.
Huang TM, Kuo KC, Wang YH, et al. Risk of active tuberculosis among COPD patients treated with fixed combinations of long-acting beta2 agonists and inhaled corticosteroids. BMC Infectious Diseases. 2020;20(1):706. doi:10.1186/s12879-020-05440-6.