(318) Comparative effectiveness and safety of single-inhaler triple therapy for COPD

Background: Current guidelines recommend triple inhaler therapy for some patients with severe chronic obstructive pulmonary disease (COPD). Two single inhaler triple therapies are currently available in the US: budesonide-glycopyrrolate-formoterol and fluticasone-umeclidinium-vilanterol. Though current guidelines do not favor one inhaler over the other, prior observational studies have suggested a lower risk of pneumonia in patients with COPD receiving budesonide- vs. fluticasone-containing inhalers. However, budesonide-glycopyrrolate-formoterol is also a metered dose inhaler (MDI) containing propellants associated with substantial greenhouse gas emissions while fluticasone-umeclidinium-vilanterol is a dry powder inhaler (DPI) with no such propellants. Many health systems now seek to promote use of DPIs over MDIs to slow climate change.

Objectives: To compare the effectiveness and safety of budesonide-glycopyrrolate-formoterol and fluticasone-umeclidinium-vilanterol in patients with COPD.

Methods: We performed a 1:1 propensity score matched observational cohort study using Optum’s de-identified Clinformatics® Data Mart. New initiators of budesonide-glycopyrrolate-formoterol (exposure) and fluticasone-umeclidinium-vilanterol (referent) between January 1, 2018 to July 31, 2023 with COPD were included in the cohort. Potential confounders were measured in the 365 days before cohort entry and included in propensity scores. The outcomes were first moderate or severe COPD exacerbation and first pneumonia hospitalization. Patients were followed for up to 1 year, the end of data, or until they experienced the outcome of interest, discontinued treatment, added or switched inhalers, died, or were disenrolled from insurance. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a Cox proportional hazards regression model. The protocol was preregistered at the Center for Open Science (https://osf.io/6gdyp/).

Results: The study included 20,128 matched initiators of the two treatments. Use of budesonide-glycopyrrolate-formoterol was associated with 12% higher rate of first moderate or severe exacerbation of COPD (HR 1.12, 95% CI 1.07-1.18) compared to fluticasone-umeclidinium-vilanterol, but a similar rate of first pneumonia hospitalization (HR 0.98, 95% CI 0.89-1.08).

Conclusions: Budesonide-glycopyrrolate-formoterol, an MDI associated with substantial greenhouse gas emissions, was also associated with a higher incidence of first COPD exacerbation compared to fluticasone-umeclidinium-vilanterol. Health systems might consider making fluticasone-umeclidinium-vilanterol the triple inhaler therapy of choice for COPD management.