Exacerbations and Real-World Outcomes After Single-Inhaler Triple Therapy of Budesonide/Glycopyrrolate/Formoterol Fumarate, Among Patients with COPD: Results from the EROS (US) Study

Abstract

Purpose: Triple therapy to prevent exacerbations from chronic obstructive pulmonary disease (COPD) is associated with improved health compared to single and dual-agent therapy in some populations. This study assessed the benefits of prompt administration of budesonide/glycopyrrolate/formoterol fumarate (BGF) following a COPD exacerbation.

Patients and methods: EROS was a retrospective analysis of people with COPD using the MORE² Registry^®. Inclusion required ≥1 severe, ≥2 moderate, or ≥1 moderate exacerbation while on other maintenance treatment. Within 12 months following the index exacerbation, ≥1 pharmacy claim for BGF was required. Primary outcomes were the rate of COPD exacerbations and healthcare costs for those that received BGF promptly (within 30 days of index exacerbation) versus delayed (31-180 days) and very delayed (181-365 days). The effect of each 30-day delay in initiation of BGF was estimated using a multivariable negative binomial regression model.

Results: 2409 patients were identified: 434 prompt, 1187 delayed, and 788 very delayed. The rate (95% CI) of total exacerbations post-index increased as time to BGF initiation increased: prompt 1.52 (1.39-1.66); delayed 2.00 (1.92-2.09); and very delayed 2.30 (2.20-2.40). Adjusting for patient characteristics, each 30-day delay in receiving BGF was associated with a 5% increase in the average number of subsequent exacerbations (rate ratio, 95% CI: 1.05, 1.01-1.08; p<0.05). Prompt initiation of BGF was also associated with lower post-index annualized COPD-related costs ($5002 for prompt vs $7639 and $8724 for the delayed and very delayed groups, respectively).

Conclusion: Following a COPD exacerbation, promptly initiating BGF was associated with a reduction in subsequent exacerbations and reduced healthcare utilization and costs.

Keywords: COPD; budesonide/glycopyrrolate/formoterol fumarate; delayed therapy; exacerbations; triple therapy.

Figure 1

Study design for Exacerbations and Real-World Outcomes (EROS) Among Chronic Obstructive Pulmonary Disease patients receiving BGF.

Figure 2

Sample selection of COPD patients, initiating BGF following a COPD exacerbation.

Figure 3

Comparison of annualized rates of subsequent COPD exacerbations, following index COPD exacerbation, by delay of BGF initiation.

Figure 4

Adjusted rate ratios (95% confidence intervals) for average number of subsequent COPD exacerbations (per-patient-per-year) following the index exacerbation. Results for negative binomial regression model, modeling for number of post-index exacerbations, controlling for Elixhauser Comorbidity Index Score, number of baseline exacerbations, presence of short-acting treatment during baseline, presence of long-acting treatment during baseline, number of baseline COPD physician visits, number of baseline pulmonologist visits, sex, payer group (commercial, Medicare Advantage, or unknown), index exacerbation type (moderate exacerbation, moderate telehealth exacerbation, or severe exacerbation), index year (2020 or 2021), presence of baseline nebulizer use, presence of baseline oxygen therapy use, presence of baseline comorbidities, including abnormal sputum, acute bronchitis, acute respiratory failure, allergic rhinitis, anxiety, asthma, cancer diagnoses other than basal or squamous cell skin cancer, cardiovascular disease, chronic cough, COVID-19, severe COVID-19, cystic fibrosis, osteoarthritis, depression, diabetes, dyspnea, fatigue, gastroesophageal reflux disease, interstitial fibrosis, osteoporosis, pneumonia, pulmonary embolism, sarcoidosis, smoking status/tobacco, and tuberculosis. All statistically significant predictors are displayed in the figure, p < 0.05 was considered significant.

Figure 5

Estimated increase in post-index COPD exacerbations for each 3-month delay in BGF initiation, by average, (lower-bound-upper-bound) adjusted rate ratios. These estimates are extrapolated from the negative binomial regression model presented in Figure 4.

Figure 6

Average post-index COPD-related healthcare expenditure by time to BGF initiation after COPD exacerbation. Total healthcare costs include total pharmacy, physician office / clinic, emergency department, urgent care, telehealth, other outpatient, skilled nursing facility, and inpatient hospital costs. COPD-related healthcare costs are based on inpatient claims with a COPD diagnosis in the primary position, and outpatient claims with a COPD diagnosis in any position. Costs reported as per-patient-per-year (PPPY) in Q1 2022 USD.