Evaluating triple ICS/LABA/LAMA therapies for COPD patients: a network meta-analysis of ETHOS, KRONOS, IMPACT, and TRILOGY studies

ABSTRACT

Objectives

In some studies comparing triple with dual combination therapies in COPD there might be a possible effect of inhaler bias resulting from different inhaler devices being used in comparator arms. The aim of this study was a quantitative synthesis by considering the studies that directly compared triple ICS/LABA/LAMA vs. either dual LABA/LAMA or ICS/LABA therapies administered at fixed-dose combination (FDC) via the same inhaler device.

Methods

A network meta-analysis was performed to assess the efficacy/safety impact of triple ICS/LABA/LAMA FDC compared with dual LABA/LAMA and ICS/LBA FDCs administered via the same inhaler device in COPD patients. The treatment ranking was reported via the surface under the cumulative ranking curve analysis (SUCRA).

Results

Data obtained from 21,909 COPD patients were extracted from the ETHOS, KRONOS, IMPACT, and TRILOGY studies, the only that fulfilled the strict inclusion criteria of this research. The weighted efficacy/safety profile resulting from SUCRA provided the following ranking in patients with low eosinophil count: ICS/LABA/LAMA>LABA/LAMA≫ICS/LABA; whereas in patients with high eosinophil count the ranking was as follows: ICS/LABA/LAMA>LABA/LAMA>ICS/LABA FDC.

Conclusion

Triple ICS/LABA/LAMA FDC and dual LABA/LAMA or ICS/LABA FDCs are characterized by specific efficacy/safety profiles in agreement with the level of blood eosinophil count at baseline.

KEYWORDS:

• COPD
• dual bronchodilation
• ICS
• LABA
• LAMA
• network meta-analysis
• triple therapy

Article highlights

• This network meta-analysis included randomized controlled trials that directly compared triple ICS/LABA/LAMA vs. either LABA/LAMA or ICS/LABA therapies administered at FDC via the same device.

• The studies that fulfilled these strict inclusion criteria were the ETHOS, KRONOS, IMPACT, and TRILOGY.

• Triple ICS/LABA/LAMA FDC was ranked as the most effective treatment in reducing the risk of exacerbation and improving lung function, regardless of the level of blood eosinophil count at baseline.

• In patients with low level of blood eosinophil count at baseline LABA/LAMA and ICS/LABA FDCs were equally effective in preventing exacerbations.

• FDCs including an ICS were affected by an increased risk of pneumonia.

• No increased cardiovascular risk was detected in the FDCs that included two bronchodilators.

Declaration of interest

L Calzetta has participated as an advisor in scientific meetings under the sponsorship of Boehringer Ingelheim and Novartis, received non-financial support from AstraZeneca, a research grant partially funded by Chiesi Farmaceutici, Boehringer Ingelheim, Novartis and Almirall, and is or has been a consultant to ABC Farmaceutici, Recipharm, Zambon, Verona Pharma and Ockham Biotech. His department was funded by Almirall, Boehringer Ingelheim, Chiesi Farmaceutici, Novartis and Zambon. M Cazzola has participated as a faculty member and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Lallemand, Mundipharma, Novartis, Pfizer, Verona Pharma, and Zambon; is or has been a consultant to ABC Farmaceutici, AstraZeneca, Chiesi Farmaceutici, Edmond Pharma, Lallemand, Novartis, Ockham Biotech, Verona Pharma, and Zambon; and his department was funded by Almirall, Boehringer Ingelheim, Novartis, and Zambon. P Rogliani participated as a lecturer and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Mundipharma and Novartis. Her department was funded by Almirall, Boehringer Ingelheim, Chiesi Farmaceutici, Novartis and Zambon. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One reviewer discloses lecture fees and/or consultancies from Alfasigma, AstraZeneca, Chiesi, BI, GSK, Merck, Novartis, Zambon, Verona Pharma. A second reviewer has performed consulting, served on advisory boards, or received travel reimbursement from Amphastar, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mylan, Novartis, Sunovion, and Theravance. This reviewer has also conducted multicenter clinical research trials for some 40 pharmaceutical companies.

Author contributions

LC, BLR, and PR were involved in the conception and design, or analysis and interpretation of the data; LC, BLR, PDM, MC, PR drafted the paper or revisited it critically for intellectual content; LC, BLR, PDM, MC, PR approved the final version to be published; LC, BLR, PDM, MC, PR agree to be accountable for all aspects of the work.

Additional information

Funding

This paper was not funded.