Background: In patients with COPD on ICS/LABA, GOLD recommends a step up to ICS/LAMA/LABA in those with exacerbations or a switch to LAMA/LABA in those with major symptoms. It is unclear if a switch to LAMA/LABA may confer greater exacerbation risk vs a step up to ICS/LAMA/LABA.

Aim: To evaluate stepping up to ICS/LAMA/LABA vs switching to LAMA/LABA or staying on ICS/LABA in KRONOS (in which 74% of patients had no recent exacerbations).

Methods: In KRONOS (NCT02497001), symptomatic patients with moderate-to-very severe COPD (exacerbations in the prior year not required) were randomized to budesonide/glycopyrronium/formoterol fumarate dihydrate 320/14.4/10 µg (BGF), glycopyrronium/formoterol fumarate dihydrate 14.4/10 µg (GFF) or budesonide/formoterol fumarate dihydrate 320/10 µg (BFF) via MDI, or budesonide/formoterol fumarate dihydrate 400/12 µg via DPI (BUD/FORM) for 24 weeks. Lung function and moderate/severe exacerbation rates were analyzed post hoc in patients on ICS/LABA in the 30 days before screening.

Results: On stepping up to BGF, while lung function was similar vs switching to GFF, exacerbation risk was substantially reduced; lung function benefits were greater and exacerbation risk was numerically reduced with BGF vs BFF or BUD/FORM (Table).

Conclusion: In this analysis, symptomatic patients on ICS/LABA had reduced exacerbation risk from a step up to ICS/LAMA/LABA vs a switch to LAMA/LABA.