Triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BGF) may reduce the risk of death compared with glycopyrrolate/formoterol fumarate (GFF) in patients with chronic obstructive pulmonary disease (COPD), according to study results published in the American Journal of Respiratory and Critical Care Medicine.1
Treatment for COPD includes bronchodilators (long-acting muscarinic antagonist [LAMA] and/or long-acting β2-agonist [LABA]), which may be combined with an inhaled corticosteroid (ICS).1 While these medications may improve lung function and symptoms and reduce the frequency of COPD exacerbations, clinical trials have provided inconsistent evidence of their benefits on mortality. In a Phase 3, 52-week clinical trial in COPD (ETHOS; ClinicalTrials.gov Identifier: NCT02465567), triple therapy with BGF significantly reduced all-cause mortality vs GFF.2 However, 384 out of 8509 participants were missing vital status at week 52 in the original analyses.
Therefore, researchers assessed the robustness of these mortality findings following additional data retrieval for patients missing week 52 vital status in the original analyses.1 In the final retrieved dataset that included week 52 vital status for 99.6% of the intent-to-treat population, the risk of death with BGF 320/18/9.6 µg was significantly lower vs GFF (hazard ratio [HR], 0.51; 95% CI, 0.33-0.80; unadjusted P =.0035). There were no significant differences in mortality when comparing BGF 320/18/9.6 µg with budesonide/formoterol fumarate (BFF; HR, 0.72; 95% CI, 0.44-1.16; 28% reduction; P =.1721), nor were significant differences observed when comparing BGF 160/18/9.6 μg against either dual comparator.
Results were similar when the first 30, 60, or 90 days of treatment were excluded from the analysis. Deaths from cardiovascular causes occurred in 0.5%, 0.8%, 1.4%, and 0.5% of patients in the BGF 320/18/9.6 µg, BGF 160/18/9.6 μg, GFF, and BFF groups, respectively.
The study authors concluded, “Regardless of the precise mechanism, our findings underscore the need to target mortality reduction as an achievable goal in the treatment of COPD, which is a leading cause of death worldwide.”1
Disclosure: This clinical trial was supported by AstraZeneca. Please see the original reference for a full list of authors’ disclosures.
1. Martinez FJ, Rabe KF, Ferguson GT, et al; on behalf of the ETHOS investigators. Reduced all-cause mortality in the ETHOS trial of budesonide/glycopyrrolate/formoterol for COPD: a randomized, double-blind, multi-center parallel-group study. Am J Respir Crit Care Med. Published online November 30, 2020. doi:10.1164/rccm.202006-2618OC
2. Rabe KF, Martinez FJ, Ferguson GT, et al; for the ETHOS Investigators. Inhaled triple therapy at two glucocorticoid doses in moderate-to-very severe COPD. N Engl J Med. 2020;383(1):35-48.