Triple therapy with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) in patients with chronic obstructive pulmonary disease (COPD), regardless of exacerbation history, reduced exacerbation rates compared with the use of glycopyrrolate/formoterol fumarate (GFF) MDI. Researchers conducted a post hoc analysis of the 24-week, double-blind, parallel-group, phase 3, randomized controlled KRONOS study (ClinicalTrials.gov identifier: NCT02497001). Results of this subgroup analysis were published in the International Journal of Chronic Obstructive Pulmonary Disease.
The investigators sought to explore whether the benefits observed with the use of BGF MDI were driven by patients who had experienced at least 1 COPD exacerbation in the prior year or were also true for those with no prior exacerbations. They analyzed lung function endpoints and rates of exacerbations post hoc in the 2 subgroups of patients with and without a COPD exacerbation in the year prior to the study. Participants received BGF MDI 320/18/9.6 µg, GFF MDI 18/9.6 µg, budesonide/formoterol fumarate (BFF) MDI 320/9.6 µg, or budesonide/formoterol fumarate dry powder inhaler (BUD/FORM DPI) 400/12 µg twice daily.
Overall, 74.4% (1411/1896) of participants in the KRONOS modified intent-to-treat population experienced no documented moderate/severe COPD exacerbations in the prior 12 months. The mean patient age in the post hoc analysis was 65.5 years; 72.8% of the participants were men. At screening, 69.9% of the participants used inhaled corticosteroids.
Results of the study showed that BGF MDI significantly decreased exacerbation rates compared with GFF MDI in the prior-exacerbations subgroup (58%; unadjusted
P =.0003) and no-prior-exacerbations subgroup (48%; unadjusted P =.0001). The magnitude of reduction in rates of COPD exacerbations was generally similar within subgroups for BGF MDI vs BFF MDI and BGF MDI vs BUD/FORM DPI.
In the subgroup who experienced prior COPD exacerbations, the risk during treatment for time to first exacerbation was significantly lower with BGF MDI vs GFF MDI
(P =.0022) and BGF MDI vs BFF MDI (P =.0110). Based on the results for BGF MDI vs GFF MDI, the number needed to treat for 1 year to prevent 1 additional moderate/severe COPD exacerbation was 3 (95% CI, 2-6) in the no prior exacerbations subgroup and 2 (95% CI, 1 to 3) in the prior exacerbations subgroup. The magnitude of decrease in exacerbation rates for BGF MDI vs GFF MDI increased with blood eosinophil counts.
The researchers concluded that the findings from this post hoc analysis suggest that the benefits on exacerbation rates reported in the KRONOS study among symptomatic patients with moderate to very severe COPD were not driven by the small subgroup of patients with a history of prior disease exacerbations.
Disclosure: This clinical trial was supported by AstraZeneca. Please see the original reference for a full list of authors’ disclosures.
Martinez FJ, Ferguson GT, Bourne E, et al. Budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler improves exacerbation outcomes in patients with COPD without a recent exacerbation history: a subgroup analysis of KRONOS. Int J Chron Obstruct Pulmon Dis. 2021;16:179-189.