Real-world data: FF/UMEC/VI offers clinical advantages over another 3-in-1 COPD inhaler
20 Aug 2025
Once-daily, single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) outperforms twice-daily, single-inhaler triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BUD/GLY/ FORM) in the treatment of chronic obstructive pulmonary disease (COPD), two recent real-world comparative effectiveness studies have found.
FF/UMEC/VI and BUD/GLY/FORM are the only two single-inhaler triple therapies approved in the US for maintenance treatment of COPD as of mid-July 2025. Their comparative effectiveness has not been established. [Adv Ther 2025;42:1131-1146; BMJ 2024;387:e080409]
FF/UMEC/VI: Lower exacerbation and mortality risks
Professor David Mannino and his team at the University of Kentucky in Lexington, Kentucky, US used data from the Komodo Research healthcare claims dataset from January 2016 to December 2023 to conduct a real-world comparative effectiveness study in a large cohort of patients with COPD newly initiated on FF/UMEC/ VI (n=33,312) or BUD/GLY/FORM (n=12,230). The mean follow-up duration was 347 and 339 days, respectively. [Adv Ther 2025;42:1131-1146]
After weighting baseline patient demographics and clinical characteristics between the two treatment groups (mean age, 73.8 years; female, 53.8 percent) to adjust for confounding, FF/ UMEC/VI was shown to significantly reduce the 12-month rate of moderate-to-severe COPD exacerbations by 12 percent (0.80 vs 0.91 per patient-year; rate ratio, 0.88; 95 percent confidence interval [CI], 0.85–0.92; p<0.001) vs BUD/GLY/FORM.
“Results were driven by moderate COPD exacerbations, which were approximately six times more frequent and approximately four times more likely than severe exacerbations,” the researchers noted. “Only a small number of severe exacerbations were observed. Therefore, the study was not powered to detect a difference in severe exacerbations between the two treatment groups.”
Notably, FF/UMEC/VI also significantly decreased the risk of all-cause mortality by 11 percent (5.6 vs 6.4 percent; hazard ratio [HR], 0.89; 95 percent CI, 0.80–0.98; p=0.020) vs BUD/GLY/ FORM.
BUD/GLY/FORM: Higher exacerbation risk
Dr William Feldman and his team at Harvard Medical School in Boston, Massachusetts, US, conducted a 1:1 propensity score–matched study, which yielded similar results. [BMJ 2024;387:e080409]
Using longitudinal commercial US claims data, they compared the effectiveness of FF/UMEC/VI (n=20,388; mean age, 70.8 years; female, 55.7 percent) and BUD/GLY/FORM (n=20,388; mean age, 70.8 years; female, 55.5 percent) in new users. The key outcome was first moderate or severe COPD exacerbation. Median follow-up duration was 88 days among patients receiving BUD/GLY/FORM and 113 days among those receiving FF/UMEC/VI.
Compared with FF/UMEC/VI, BUD/ GLY/FORM was associated with a 9 percent higher risk of first moderate or severe COPD exacerbation (HR, 1.09; 95 percent CI, 1.04–1.14), with a number needed to harm of 38.
When analyzing moderate and severe COPD exacerbations separately, BUD/GLY/FORM was associated with a 29 percent higher risk of first severe exacerbation (HR, 1.29; 95 percent CI, 1.12–1.48; number needed to harm, 97) and a 7 percent higher risk of first moderate COPD exacerbation (HR, 1.07; 95percent CI, 1.02–1.12; number needed to harm, 54) vs FF/UMEC/VI.
At-risk subgroups
Across most subgroups, patients receiving BUD/GLY/FORM had a slightly higher risk of first moderate or severe COPD exacerbation vs FF/UMEC/VI, including:
- Global Initiative for Chronic Obstructive Lung Disease (GOLD) group E (HR, 1.07; 95 percent CI, 1.01–1.13);
- GOLD group A/B (HR, 1.09; 95 percent CI, 1.01–1.18);
- ≥1 moderate or severe exacerbations at baseline (HR, 1.15; 95 percent CI, 1.04–1.28);
- Use of maintenance inhalers before starting triple therapy (HR, 1.14; 95 percent CI, 1.08–1.20);
- Prior diagnosis of asthma (HR, 1.09; 95 percent CI, 1.02–1.16);
- No recent diagnosis of asthma within 3 years (HR, 1.07; 95 percent CI, 1.01– 1.13);
- Eosinophil count >300 cells/μL (HR, 1.20; 95 percent CI, 1.02–1.41);
- Underwent spirometry during the baseline assessment (HR, 1.08; 95 percent CI, 1.01–1.16);
- Index prescription from a pulmonologist (HR, 1.09; 95 percent CI, 1.04–1.14). [BMJ 2024;387:e080409]
Adherence and delivery devices may play a role
“Higher treatment adherence could partially explain the more favourable outcomes observed among FF/UMEC/VI users,” Mannino’s team explained. A recent US real-world study evaluated treatment patterns in patients with COPD who received either FF/UMEC/VI (n=8,912) or BUD/GLY/FORM (n=2,685). Adherence was assessed as the mean proportion of days covered. Results showed that adherence rates were significantly higher among initiators of FF/UMEC/VI vs those starting BUD/GLY/FORM at both 6 and 12 months post-index. [Adv Ther 2025;42:1131-1146; Adv Ther 2024;42:830-848]
“Improved adherence to FF/UMEC/ VI may be due to its simplified regimen, which involves only one inhalation daily vs two inhalations daily for BUD/GLY/ FORM,” Mannino’s team added. “This may be especially relevant for older patients who have lower treatment adherence and may skip doses [eg, in the middle of the day] due to forgetfulness.”
Apart from adherence, Feldman and his team proposed other potential explanations. Different techniques are required to operate the two inhalers: Metered dose inhalers require patients to time their breaths with actuation, whereas dry powder inhalers require only deep inspiration. “Research has suggested lower error rates with dry powder inhalers containing FF/ UMEC/VI than metered dose inhalers,” they stated. “[Additionally,] the active moieties in FF/UMEC/VI could be more effective in preventing COPD exacerbations than those in BUD/GLY/FORM.” [BMJ 2024;387:e080409]
Environmental considerations
Metered-dose inhalers are associated with substantially higher greenhouse gas emissions vs dry powder inhalers, and they account for approximately 3 percent of the National Health Service carbon footprint in the UK. [PLoS Med 2025;22:e1004596; BMJ 2024;387:e080409]
“Since BUD/GLY/FORM did not demonstrate improved clinical outcomes vs FF/UMEC/VI, and given the environmental concerns associated with metered dose inhalers, health systems looking to decrease use of metered dose inhalers may consider increasing prescriptions of FF/UMEC/VI over BUD/GLY/FORM for patients with COPD,” suggested Feldman and his team.
