Abstract

BackgroundLong-term use of inhaled corticosteroids (ICSs) has been associated with increased risk of bone and ocular comorbidities. We evaluated the effects of the triple fixed-dose combination budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI), formulated using co-suspension delivery technology, on bone mineral density (BMD) and ocular safety in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD).MethodsIn this extension study, a subset of patients from the 24-week, phase III, randomized, double-blind KRONOS study (NCT02497001) continued treatment (BGF MDI 320/18/9.6 μg, budesonide/formoterol fumarate [BFF] MDI 320/9.6 μg or glycopyrrolate/formoterol fumarate [GFF] MDI 18/9.6 μg, as a non-steroidal comparator) for an additional 28 weeks. Primary endpoints were percentage change from baseline in lumbar spine BMD and change from baseline in lens opacities classification system III posterior subcapsular cataract (P) score, both at Week 52. Adverse events were also assessed.ResultsIn total, 456 patients were included in the safety population (53.1% male, mean age 62.8 years). Changes from baseline in lumbar spine BMD (least squares mean [LSM] range − 0.12 to 0.38%) and P score (LSM range 0.02–0.15) were small for all treatments. Both BGF MDI and BFF MDI were non-inferior to GFF MDI using margins of −2% (BMD) and 0.5 units (P score). The incidence of treatment-emergent adverse events (TEAEs) was generally similar among groups. Rates of confirmed pneumonia were low overall (2.4%) and highest in the GFF MDI group (3.4%), followed by BGF MDI (2.1%) and BFF MDI (1.1%). There were no cumulative adverse effects of treatment over time as the incidence and types of TEAEs, were generally similar in the first 24 weeks of the study and after Week 24.ConclusionsIn patients with COPD, both ICS-containing therapies were non-inferior to GFF MDI for the primary BMD and ophthalmological endpoints. Changes from baseline in all three treatment groups over 52 weeks were small and not clinically meaningful. All treatments were well tolerated with no new or unexpected safety findings.Trial registrationClinicalTrials.gov NCT02536508. Registered 27 August 2015.

Highlights

  • Treatment with long-acting bronchodilators is central to the management of chronic obstructive pulmonary disease (COPD) [1]

  • Study population In total, 627 patients who were randomized in KRONOS consented to participate in the extension study (Fig. 1)

  • Overall, this study found no clinically meaningful differences in bone mineral density (BMD) or ophthalmological safety assessments over 52 weeks after treatment with inhaled corticosteroid (ICS)-containing therapies Budesonide/ glycopyrrolate/formoterol fumarate (BGF) Metered dose inhaler (MDI) and budesonide/formoterol fumarate (BFF) MDI compared to the Long-acting antimuscarinic antagonist (LAMA)/Long-acting β2-agonist (LABA) glycopyrrolate/formoterol fumarate (GFF) MDI

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Summary

Introduction

Treatment with long-acting bronchodilators is central to the management of chronic obstructive pulmonary disease (COPD) [1]. Concerns remain regarding possible consequences of long-term ICS use, including decreased bone density and the development of cataracts. These are especially relevant for patients with COPD as the majority are older adults [4], and risk of bone loss and ocular comorbidities increases with age [5, 6]. We evaluated the effects of the triple fixed-dose combination budesonide/ glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI), formulated using co-suspension delivery technology, on bone mineral density (BMD) and ocular safety in patients with moderate-tovery severe chronic obstructive pulmonary disease (COPD)

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