Frequent productive cough in COPD relates to exacerbation risk and treatment benefit from budesonide/glycopyrrolate/formoterol fumarate: a post hoc analysis of KRONOS.

BACKGROUND

Frequent productive cough (FPC) is associated with increased exacerbation risk in chronic obstructive pulmonary disease (COPD). These post hoc analyses examined COPD exacerbations in participants without a recent exacerbation history by baseline FPC status (defined as COPD Assessment Test [CAT] subscores ≥2 for both cough and sputum) and for budesonide/glycopyrrolate/formoterol fumarate (BGF) versus dual therapies.

METHODS

KRONOS (NCT02497001) was a 24-week, double-blind, parallel-group, multi-center, Phase III, randomized study in symptomatic people with moderate-to-very severe COPD; COPD exacerbation in the preceding 12 months was not required. Participants were randomized 2:2:1:1 to receive BGF 320/18/9.6 μg, glycopyrrolate/formoterol fumarate (GFF) 18/9.6 μg, budesonide/formoterol fumarate (BFF) 320/9.6 μg via metered-dose inhaler, or open-label budesonide/formoterol fumarate 400/12 μg via dry-powder inhaler (BUD/FORM), as two inhalations twice-daily.

RESULTS

Of 1411 participants in the modified intent-to-treat population without a recent COPD exacerbation history, 965 (68.4 %) had baseline FPC. Moderate/severe exacerbation rates were higher in those with versus without FPC (BGF, 0.47 vs 0.29; BFF, 0.45 vs 0.37; BUD/FORM, 0.67 vs 0.14), except for GFF (0.79 vs 0.83). BGF was associated with reduced moderate/severe exacerbation rates among those with FPC (41 % reduction) and without FPC (65 % reduction) at baseline versus GFF, with similar findings observed in moderate COPD (FPC: 37 % reduction; without FPC, 72 % reduction).

CONCLUSIONS

Among participants without an exacerbation history in the prior 12 months, FPC identified those at higher exacerbation risk. Further, BGF was associated with lower COPD exacerbation rates versus GFF, including numerically lower among those with moderate COPD and regardless of FPC status.

CLINICAL TRIAL REGISTRATION: NCT02497001.