Ferguson GT, et al. - In symptomatic patients with moderate to very severe chronic obstructive pulmonary disease (COPD), authors sought to compare the efficacy of a triple therapy with corresponding dual therapies, without a requirement for a history of exacerbations. Compared to the corresponding dual therapies, budesonide/glycopyrrolate/formoterol fumarate metered-dose inhaler 320/18/9·6 μg (BGF MDI) was efficacious, well tolerated, and could be a more appropriate treatment for symptomatic patients with moderate to very severe COPD, irrespective of exacerbation history.

Methods

• Researchers recruited patients from hospitals and care centres in Canada, China, Japan, and the USA in this double-blind, parallel-group, multicentre phase 3 randomised controlled trial.
• The age of the ligible patients was 40–80 years, they were current or former smokers (with a smoking history of ≥10 pack-years), had an established clinical history of COPD, and were symptomatic for COPD, despite receiving two or more inhaled maintenance therapies for at least 6 weeks before screening.
• Using an interactive web response system, patients were randomly assigned (2:2:1:1) to receive budesonide/glycopyrrolate/formoterol fumarate metered-dose inhaler 320/18/9·6 μg (BGF MDI), glycopyrrolate/ formoterol fumarate metered-dose inhaler 18/9·6 μg (GFF MDI), budesonide/formoterol fumarate metered-dose inhaler 320/9·6 μg (BFF MDI), or open-label budesonide/formoterol fumarate dry-powder inhaler 400/12 μg (BUD/ FORM DPI).
• For the Europe/Canada statistical analysis approach primary endpoints were FEV₁ area under the curve from 0-4 h (AUC0-4) for BGF MDI vs BFF MDI and BGF MDI vs BUD/FORM DPI over 24 weeks; and change from baseline in morning pre-dose trough FEV₁ for BGF MDI vs GFF MDI and non-inferiority of BFF MDI vs BUD/FORM DPI (margin of -50 mL from lower bound of 95% CI) over 24 weeks.
• Only for the Europe/Canada statistical analysis approach, they made comparisons with BUD/FORM DPI.

Results

• Between Aug 20, 2015, and Jan 5, 2018, 3047 patients were screened from 215 sites, and 1902 were randomly assigned to receive BGF MDI (n=640), GFF MDI (n=627), BFF MDI (n=316), or BUD/FORM DPI (n=319).
• Over 24 weeks, significant improvement in FEV₁AUC_0–4vs BFF MDI (least squares mean difference 104 mL, 95% CI 77 to 131; p < 0·0001) and BUD/FORM DPI (91 mL, 64 to 117; p < 0·0001) was seen with BGF MDI.
• Results demonstrated that BGF MDI also significantly improved pre-dose trough FEV₁ vs GFF MDI (22 mL, 4 to 39; p=0·0139) and was non-inferior to BUD/FORM DPI (μ10 mL, μ36 to 16; p=0·4390).
• At week 24, a significantly improved FEV₁ AUC_0–4 was seen in the patients in the BGF MDI group vs with patients receiving BFF MDI (116 mL, 95% CI 80 to 152; p < 0·0001); there was a non-significant improvement in the change from baseline in morning pre-dose trough FEV₁at week 24 vs GFF MDI (13 mL, μ9 to 36 mL; p=0·2375).
• Findings suggested the most common treatment-emergent adverse events to be nasopharyngitis (n=49 [8%] in the BGF MDI group; n=41 [7%] in the GFF MDI group; n=26 [8%] in the BFF MDI group; and n=30 [9%] in the BUD/FORM DPI group) and upper respiratory tract infection (n=65 [10%]; n=38 [6%]; n=18 [6%]; and n=22 [7%]).
• Across treatments, pneumonia incidence was low (<2%) and similar.
• Both in the GFF MDI group, two treatment-related deaths were seen.