Guidelines for the treatment of chronic obstructive pulmonary disease (COPD) patients with multiple exacerbations and eosinophilia recommend a long-acting beta₂-agonist (LABA) and inhaled corticosteroid (ICS) combined inhaler, with no distinction between different agents. We compared the effectiveness and safety of budesonide-formoterol versus fluticasone-salmeterol on the incidence of exacerbations and pneumonia in a real-world clinical practice setting of COPD, particularly considering eosinophilia, an important marker for ICS effectiveness.

We identified a cohort of patients with COPD, new users of a LABA-ICS during 2002–2018, age 50 or older, from the UK's CPRD database, and followed for one year. The hazard ratio (HR) of exacerbation and of pneumonia was estimated using the Cox regression model, weighted by fine stratification of the propensity score of treatment initiation.

The cohort included 24,973 of budesonide-formoterol and 61,251 initiators of fluticasone-salmeterol. The adjusted HR of a first moderate or severe exacerbation with budesonide-formoterol relative to fluticasone-salmeterol was 0.98 (95% CI: 0.95–1.01), while for severe exacerbation it was 0.92 (95% CI: 0.85–0.99). The HR of severe pneumonia with budesonide-formoterol was 0.76 (95% CI: 0.70–0.83), and was particularly decreased with higher blood eosinophil count, dropping to 0.62 (95% CI: 0.51–0.77) at >300 cells/μL.

In a real-world clinical setting of COPD treatment, a budesonide-formoterol inhaler was generally as effective at reducing the incidence of moderate-severe exacerbations as fluticasone-salmeterol. However, budesonide-formoterol was more effective than fluticasone-salmeterol at reducing the incidence of severe exacerbation and the risk of severe pneumonia, particularly in patients with higher blood eosinophil counts.