Asthma management with triple ICS/LABA/LAMA combination to reduce the risk of exacerbation: an umbrella review compliant with the PRIOR statement

ABSTRACT

Introduction

According to Global Initiative for Asthma (GINA) guidelines, long-acting muscarinic antagonists (LAMAs) should be considered as add-on therapy in patients with asthma that remains uncontrolled, despite treatment with medium-dose (MD) or high-dose (HD) inhaled corticosteroids (ICS)/long-acting β₂-agonist (LABA) combinations. In patients ≥ 18 years, LAMA may be added in triple combination with an ICS and a LABA. To date, the precise efficacy of triple ICS/LABA/LAMA combination remains uncertain concerning the impact on exacerbation risk in patients with uncontrolled asthma. Therefore, an umbrella review was performed to systematically summarize available data on the effect of triple ICS/LABA/LAMA combination on the risk of asthma exacerbation.

Methods

An umbrella review has been performed according to the PRIOR statement.

Results

The overall results obtained from 5 systematic reviews and meta-analyses suggest that triple ICS/LABA/LAMA combination reduces the risk of asthma exacerbation. HD-ICS showed a greater effect particularly in reducing severe asthma exacerbation, especially in patients with evidence of type 2 inflammation biomarkers.

Conclusions

The findings of this umbrella review suggest an optimization of ICS dose in triple ICS/LABA/LAMA combination, based on the severity of exacerbation and type 2 biomarkers expression.

KEYWORDS:

• Asthma
• exacerbation
• triple combination
• umbrella review
• type 2 biomarkers

Article highlights

• The overall results obtained from the umbrella review suggest that triple ICS/LABA/LAMA combination reduces the risk of asthma exacerbation.

• HD-ICS showed a greater effect in reducing severe asthma exacerbation, especially in patients with evidence of type 2 inflammation biomarkers.

• Despite it is possible to characterize the treatable traits of asthmatic patients in order to optimize the use of triple ICS/LABA/LAMA combination therapy, the decision of switching to triple ICS/LABA/LAMA combination or escalating to HD-ICS/LABA combination, in patients poorly controlled with MD-ICS/LABA combination, remains a clinical challenge.

Declaration of Interest

L Calzetta declares grants and personal fees from Boehringer Ingelheim, grants and personal fees from Novartis, nonfinancial support from AstraZeneca, grants from Chiesi Farmaceutici, grants from Almirall, personal fees from ABC Farmaceutici, personal fees from Edmond Pharma, grants and personal fees from Zambon, personal fees from Verona Pharma, and personal fees from Ockham Biotech.

P Rogliani declares grants and personal fees from Boehringer Ingelheim, grants and personal fees from Novartis, personal fees from AstraZeneca, grants and personal fees from Chiesi Farmaceutici, grants and personal fees from Almirall, grants from Zambon, personal fees from Biofutura, personal fees from GlaxoSmithKline, personal fees from Menarini, and personal fees from Mundipharma.

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.

Author contributions

R Laitano: data curation, visualization, writing—original draft, writing—review & editing.

L Calzetta: conceptualization, data curation, funding acquisition, methodology, project administration, resources, software, supervision, visualization, writing—original draft, writing— review & editing.

M Matino: data curation, visualization, writing—original draft, writing—review & editing.

E Pistocchini: data curation, visualization, writing—original draft, writing—review & editing.

P Rogliani: conceptualization, data curation, funding acquisition, methodology, project administration, resources, software, supervision, visualization, writing—original draft, writing— review & editing.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.