Risk of sepsis among patients with COPD treated with fixed combinations of inhaled corticosteroids and long-acting Beta2 agonists

Abstract

This study aimed to compare the effect of budesonide/formoterol and fluticasone/salmeterol on the risk and outcomes of sepsis in COPD patients. We conducted this study using the Taiwan National Health Insurance Research Database. We included COPD patients prescribed with budesonide/formoterol or fluticasone/salmeterol between 2004 and 2011. Outcomes including sepsis and mortality were measured. 10,267 COPD patients who received fluticasone/salmeterol and 6,844 patients who received budesonide/formoterol were enrolled into this study and then subsequence were adjusted by propensity score weighting. The incidence of sepsis was 5.74 and 4.99 per 100 person-years for the patients receiving fluticasone/salmeterol and budesonide/formoterol, respectively. Fluticasone/salmeterol was associated with higher risk of sepsis (aHR, 1.15; 95%CI, 1.07-1.24) and septic shock (aHR, 1.14; 95%CI, 1.01-1.29) than budesonide/formoterol. Besides, fluticasone/salmeterol was associated with higher risk of death (aHR, 1.090; 95%CI, 1.01-1.18) than budesonide/formoterol. Patients receiving fluticasone/salmeterol had a significant higher risk of sepsis related respiratory organ dysfunction, lower respiratory tract infection, genitourinary tract infection, bacteremia and skin infection. In conclusion, long-term treatment with budesonide/formoterol was associated with lower rates of sepsis and deaths than fluticasone/salmeterol in patients with COPD.

Risk of active tuberculosis among COPD patients treated with fixed combinations of long-acting beta2 agonists and inhaled corticosteroids

“…Even in the subgroup analysis, the fluticasone/salmeterol group remained associated with a higher risk of active TB compared with the budesonide/ formoterol group. This intra-class difference has been shown in a previous study [21], and there may be different risks for other infectious diseases between budesonide/formoterol and fluticasone/salmeterol. In the PATHOS study, the rate of pneumonia and the pneumonia event rate per 100 patients were higher in fluticasone/salmeterol compared with budesonide/formoterol [19].…”

“…In the PATHOS study, the rate of pneumonia and the pneumonia event rate per 100 patients were higher in fluticasone/salmeterol compared with budesonide/formoterol [ 19 ]. Another study showed that fluticasone/salmeterol carried a higher risk of sepsis (aHR, 1.15; 95%CI, 1.07–1.24) and septic shock (aHR, 1.14; 95%CI, 1.01–1.29) compared with budesonide/formoterol [ 21 ]. However, the present study is the first to confirm an intra-class difference for the risk of active TB between fluticasone/salmeterol and budesonide/formoterol.…”

“…Although many LABA/ICS combinations have been developed, clinical experience using budesonide/formoterol and fluticasone/salmeterol, as well as associated studies, are most plentiful because these two combinations were developed earliest. Recently, several studies have revealed safety differences between fluticasone/salmeterol and budesonide/formoterol [19][20][21]. These studies found that fluticasone/salmeterol users have a higher risk of pneumonia, sepsis, and death compared with budesonide/formoterol users [19][20][21].…”

“…Recently, several studies have revealed safety differences between fluticasone/salmeterol and budesonide/formoterol [19][20][21]. These studies found that fluticasone/salmeterol users have a higher risk of pneumonia, sepsis, and death compared with budesonide/formoterol users [19][20][21]. However, no study has previously compared the risk of TB between fluticasone/salmeterol and budesonide/formoterol.…”

Capsule Commentary on Griffith et al., Overuse and Misuse of Inhaled Corticosteroids Among Veterans with COPD: a Cross-Sectional Study Evaluating Targets for De-implementation

“…1 Not only can inhaled corticosteroids lead to increased rates of pneumonia; certain combinations have been associated with higher rates of sepsis, bacteremia, and skin infections among patients with COPD. [2][3][4] Questions that arise from this research include the following: Can we systematically enhance primary care providers' knowledge and experience with COPD management and align prescribing practice with more rigorous disease phenotypes while offering an algorithm of options for treatment for patients with dyspnea from other comorbidities? Can we build an educational program that is broadly generalizable to wide sectors of the population where pharmaceutical influence has traction and seeks to sell prescriptions?…”