Comparative Efficacy of Single-Inhaler Triple Therapies in COPD

Key Takeaways

• Fluticasone furoate/vilanterol/umeclidinium was the regimen specifically reported as having significant trough FEV1 advantages in the network comparison.
• Fluticasone furoate/vilanterol/umeclidinium, budesonide/formoterol/glycopyrronium, and free triple therapy improved total SGRQ versus dual therapy, while fluticasone furoate/vilanterol/umeclidinium and free triple therapy showed borderline improvement versus beclomethasone/formoterol/glycopyrronium.
• The authors described available single-inhaler and free triple therapies as broadly similar for effectiveness and safety, although certainty was limited by the absence of direct comparisons.

In a network meta-analysis of 12 randomized trials involving 28,930 patients with COPD, fluticasone furoate/vilanterol/umeclidinium was statistically significantly more effective at increasing trough FEV1 than dual therapies, free triple therapy, budesonide/formoterol fumarate/glycopyrronium bromide, and beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide. The comparison relied on indirect links across randomized studies rather than direct head-to-head trials among the regimens. Broader efficacy and safety findings were otherwise described as largely similar across triple-therapy approaches.

This systematic review and network meta-analysis evaluated COPD single-inhaler triple therapies after database searches through November 2025 limited to English-language articles. Eligible studies were randomized trials lasting at least 12 weeks and enrolling at least 300 participants. The investigators defined single-inhaler triple therapy as ICS/LABA/LAMA, free triple therapy as ICS/LABA+LAMA, and dual therapy as ICS/LABA or LABA/LAMA. Prespecified outcomes included trough FEV1, moderate and severe exacerbations, SGRQ total score, SGRQ responders, TDI focal score, and safety. The analysis was designed to compare the available regimen classes across symptom, lung-function, exacerbation, and safety measures in a single framework.

For lung function, fluticasone furoate/vilanterol/umeclidinium was statistically significantly more effective at increasing trough FEV1 than dual therapies, free triple therapy, budesonide/formoterol fumarate/glycopyrronium bromide, and beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide. Investigators also reported significant improvement in total SGRQ score versus dual therapy for fluticasone furoate/vilanterol/umeclidinium, budesonide/formoterol fumarate/glycopyrronium bromide, and free triple therapy. Fluticasone furoate/vilanterol/umeclidinium and free triple therapy also showed borderline significant SGRQ improvement versus beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide. These patient-reported findings favored several options over dual therapy, but not every reported comparison separated clearly across triple formulations.

The authors described the four available single-inhaler triple therapies and free triple therapy as having similar effectiveness and safety overall. That conclusion was qualified by the absence of direct comparison studies, which limited certainty in distinguishing differences among regimens with confidence. The authors also stated that stronger comparative interpretation will depend on further analysis as additional evidence becomes available. The overall conclusion remained cautious, pairing broader similarity with a need for more direct comparative evidence.