Post-hoc analysis of the phase 3 KRONOS study concluded that the benefits in COPD exacerbation seen were not driven by the small subgroup with a prior history of exacerbations.
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.
The findings are from a post-hoc analysis of the 24-week, double-blind, phase 3, randomized controlled KRONOS study.
Given the high proportion of patients in the original trial with no prior disease exacerbations, the authors wrote, this analysis was to investigate whether the exacerbation benefit observed with the use of BGF MDI in the overall KRONOS population was driven by the small subset of patients who had experienced ≥1 exacerbation in the year prior to the study or was also true for patients with no prior exacerbations.
Results of this subgroup analysis were published in the International Journal of Chronic Obstructive Pulmonary Disease.
KRONOS Inclusion Criteria
Eligible patients were 40–80 years of age, with a smoking history of ≥10 pack-years (current or former smokers), a confirmed diagnosis of moderate-to-very severe COPD, as defined by a post-bronchodilator FEV1 25–80% predicted, and were symptomatic (CAT score ≥10) despite treatment with ≥2 inhaled maintenance therapies for at least 6 weeks before screening.
KRONOS study patients 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. Exacerbation and lung function results from patients with and without a documented exacerbation in the 12 months prior to the study were submitted to post hoc analysis.
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.
Among participants in the KRONOS modified intent-to-treat population overall, 74.4% (1411/1896) experienced no documented moderate/severe COPD exacerbations in the 12 preceding months. 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-exacerbation subgroup (48%; unadjusted P =.0001). The magnitude of reduction in rates of COPD exacerbation 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 (NNT) 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, 1-3) in the prior-exacerbations subgroup.
Notably, 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.
