Fluticasone- vs Budesonide-Based Dual Therapy for COPD.JAMA Netw Open 2026 Mar 02; 9(3):e260959.JN
Importance
Inhaled corticosteroid (ICS)-long-acting β-agonist (LABA) inhalers are generally considered therapeutically equivalent when treating chronic obstructive pulmonary disease (COPD). However, metered-dose inhalers in the class are associated with substantially higher greenhouse gas emissions than dry powder formulations, and studies have raised questions about potential intraclass differences in clinical outcomes among patients receiving ICS-LABAs.
Objective
To analyze COPD exacerbations and pneumonia hospitalizations associated with once-daily fluticasone furoate-vilanterol dry powder inhalers, twice-daily fluticasone propionate-salmeterol dry powder inhalers, and twice-daily budesonide-formoterol metered-dose inhalers in adults with COPD.
Design, Setting, and Participants
This cohort study was conducted using longitudinal commercial claims data of US adults aged 40 years or older with COPD. Patients were 1:1 pairwise propensity score matched into 3 cohorts: (1) new users receiving fluticasone furoate-vilanterol vs budesonide-formoterol between January 1, 2014, and February 29, 2024; (2) new users receiving fluticasone furoate-vilanterol vs fluticasone propionate-salmeterol between January 1, 2014, and February 29, 2024; and (3) new users receiving fluticasone propionate-salmeterol vs budesonide-formoterol between January 1, 2007, and February 29, 2024.
Exposures
Receipt of a once-daily fluticasone furoate-vilanterol dry powder inhaler (Breo Ellipta; GSK), twice-daily fluticasone propionate-salmeterol dry powder inhaler (Advair Diskus; GSK), or twice-daily budesonide-formoterol metered-dose inhaler (Symbicort; AstraZeneca).
Main Outcomes and Measures
The primary outcomes were first moderate or severe COPD exacerbation and first pneumonia hospitalization. Hazard ratios and 95% CIs were estimated using Cox proportional hazards regression models.
Results
The cohorts included 38 070 matched pairs of patients receiving fluticasone furoate-vilanterol vs budesonide-formoterol (58.8% women; mean [SD] age, 71.0 [9.0] years), 20 471 matched pairs of patients receiving fluticasone furoate-vilanterol vs fluticasone propionate-salmeterol (58.3% women; mean [SD] age, 69.9 [9.2] years), and 55 627 matched pairs of patients receiving fluticasone propionate-salmeterol vs budesonide-formoterol (56.2% women; mean [SD] age, 68.3 [9.0] years). Patients receiving fluticasone furoate-vilanterol had a 9% lower risk of moderate or severe COPD exacerbations compared with those receiving budesonide-formoterol (hazard ratio [HR], 0.91 [95% CI, 0.88-0.94]; number needed to treat [NNT] = 40) and a 6% lower risk compared with those receiving fluticasone propionate-salmeterol (HR, 0.94 [95% CI, 0.89-0.98]; NNT = 40). The risk of moderate or severe COPD exacerbation was similar for patients receiving fluticasone propionate-salmeterol and budesonide-formoterol (HR, 0.98 [95% CI, 0.95-1.01]). No differences were observed in the risk of pneumonia hospitalization across the 3 cohorts (fluticasone furoate-vilanterol vs budesonide-formoterol: HR, 1.03 [95% CI, 0.96-1.11]; fluticasone furoate-vilanterol vs fluticasone propionate-salmeterol: HR, 0.93 [95% CI, 0.85-1.03]; and fluticasone propionate-salmeterol vs budesonide-formoterol: HR, 1.04 [95% CI, 0.98-1.10]).
Conclusions and Relevance
In this cohort study of new ICS-LABA users with COPD, once-daily dry powder fluticasone furoate-vilanterol inhalers were associated with slightly improved clinical outcomes compared with twice-daily metered-dose budesonide-formoterol inhalers and twice-daily dry powder fluticasone propionate-salmeterol inhalers. Further studies are needed to explore potential intraclass differences among inhalers used to treat COPD.
