Background: The first generic maintenance inhaler to receive Food and Drug Administration (FDA) approval was the dry-powder inhaler (DPI) Wixela Inhub (fluticasone-salmeterol) in 2019. The FDA applies a special “weight-of-evidence” approach when determining bioequivalence of complex generic products like DPIs.
Objectives: We analyzed whether new users of generic fluticasone-salmeterol with chronic obstructive pulmonary disease (COPD) had an increased incidence of first moderate or severe COPD exacerbations compared to new users of brand-name fluticasone-salmeterol when prescribed these inhalers in routine clinical practice.
Methods: A 1:1 propensity score matched observational cohort study was performed using Optum’s de-identified Clinformatics® Data Mart. Patients were included in the cohort if they had a diagnosis of COPD, were over the age of 40, and newly initiated generic fluticasone-salmeterol (Wixela Inhub) (exposure) or brand-name fluticasone-salmeterol (Advair Diskus) (referent) between January 1, 2018 and June 30, 2021. Confounders, including measures of disease severity, co-morbidities, and healthcare use, were measured in the 180 days before cohort entry and included in propensity scores. The primary outcome was first moderate or severe COPD exacerbation. Patients were followed for up to one year or until experiencing a COPD exacerbation, discontinuation of treatment (with a grace period of 60 days between prescription fills), switching from referent to exposure (or vice-versa), death, the end of insurance coverage, or June 30, 2021 (whichever occurred first). A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Several prespecified subgroup and sensitivity analyses were performed, including an analysis with 1:1 high-dimensional propensity score (hdPS) matching. The protocol was preregistered at the Center for Open Science Real World Evidence Registry (available at https://osf.io/v89qz).
Results: Among 45,369 patients (27,305 Advair Diskus users and 18,064 Wixela Inhub users), 10,012 matched pairs were identified for the primary analysis. Compared to Advair Diskus use, Wixela Inhub was associated with a similar incidence of first moderate or severe COPD exacerbations (HR 0.97, 95% CI 0.90-1.04). On sensitivity analysis using 1:1 hdPS matching, the HR for first moderate or severe exacerbation was 0.99 (95% CI 0.86-1.15).
Conclusions: Use of generic fluticasone-salmeterol was not associated with an increased incidence of first moderate or severe COPD exacerbation compared to use of brand-name fluticasone-salmeterol.
