The comparative effectiveness and safety of fluticasone-salmeterol via metered-dose versus dry powder inhalers for COPD: A new user cohort study.

Abstract

Background: Fluticasone-salmeterol is available in both metered-dose and dry powder inhaler formulations for the treatment of chronic obstructive pulmonary disease (COPD). Metered-dose inhalers are associated with substantially higher greenhouse gas emissions than dry powder inhalers; however, data on their comparative effectiveness and safety in COPD remain limited. We aimed to compare the effectiveness and safety of fluticasone-salmeterol delivered via metered-dose inhaler (Advair HFA) versus dry powder inhaler (Advair Diskus) among patients with COPD treated in routine care.

Methods and findings: We conducted a retrospective cohort study using Optum's de-identified Clinformatics DataMart (January 1, 2007 to November 30, 2023). The study included 202,052 commercially insured patients aged 40 years or older with COPD who had continuous insurance coverage for 180 days prior to cohort entry and had not initiated any inhaled corticosteroid-long-acting β₂-agonist during that period. Patients receiving fluticasone-salmeterol via a metered-dose inhaler (exposure) were compared to those receiving these drugs via a dry powder inhaler (referent), with stabilized inverse probability of treatment weighting applied for covariate adjustment. The primary effectiveness outcome was the incidence of first moderate or severe COPD exacerbation within 365 days of cohort entry. The primary safety outcome was the incidence of first pneumonia hospitalization during the same period. Use of fluticasone-salmeterol via metered-dose inhaler was associated with a similar hazard of first moderate or severe COPD exacerbation (hazard ratio [HR], 1.03; 95% confidence interval [CI], 0.99 to 1.08) and first pneumonia hospitalization (HR, 1.06; 95% CI, 0.98 to 1.14) compared to the dry powder inhaler. Primary study limitations include potential residual confounding despite weighting and short follow-up times.

Conclusions: In this cohort study comparing two brand-name fluticasone-salmeterol inhalers prescribed for COPD in routine clinical practice, effectiveness and safety outcomes were similar for patients receiving metered-dose and dry powder versions.