Single-inhaler triple vs single-inhaler dual therapy in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized control trials

Huanyu Long,Yanfei Guo,Hongxuan Xu,Jean-Paul Janssens

doi:10.1186/s12931-021-01794-w

Abstract

BackgroundIn some RCTs comparing triple therapy with dual therapy in COPD, there might be a bias resulting from the use of multiple inhaler devices. This meta-analysis included only RCTs that compared ICS/LABA/LAMA vs. LABA/LAMA or ICS/LABA using a single device.MethodsWe systematically reviewed randomized controlled trials (RCTs) of single-inhaler triple therapy in patients with COPD. We searched the PubMed, MEDLINE (OvidSP), EMBASE and Cochrane Library databases to investigate the effect of single-inhaler triple therapy in COPD. The primary end points were the effect of single-inhaler triple therapy compared with single-inhaler dual therapy on all-cause mortality, the risk of acute exacerbation of COPD (AECOPD), and some safety endpoints. The Cochrane Collaboration tool was used to assess the quality of each randomized trial and the risk of bias.ResultsA total of 25,171 patients suffering from COPD were recruited for the 6 studies. This meta-analysis indicated that single-inhaler triple therapy resulted in a significantly lower rate of all-cause mortality than LABA/LAMA FDC (risk ratio, 0.70; 95% CI 0.56‐0.88). Single-inhaler triple therapy reduced the risk of exacerbation and prolonged the time to first exacerbation compared with single-inhaler dual therapy. The FEV1 increased significantly more under single-inhaler triple therapy than under ICS/LABA FDC (mean difference, 103.4 ml; 95% CI 64.65‐142.15). The risk of pneumonia was, however, significantly higher with ICS/LAMA/LABA FDC than with LABA/LAMA FDC (risk ratio, 1.55; 95% CI 1.35–1.80).ConclusionsThis meta-analysis suggests that single-inhaler triple therapy is effective in reducing the risk of death of any cause and of moderate or severe exacerbation in COPD patients. However, the risk of pneumonia is higher with ICS/LAMA/LABA FDC than with LABA/LAMA FDC.Trial registration PROSPERO #CRD42020186726.

Highlights

In some Randomized controlled trial (RCT) comparing triple therapy with dual therapy in Chronic obstructive pulmonary disease (COPD), there might be a bias resulting from the use of multiple inhaler devices
A total of 25,171 COPD patients were recruited for these 6 studies: 11,420 patients were treated with single-inhaler triple therapy, 5,588 patients were treated with Long-acting beta2-agonist (LABA)/ Long-acting muscarinic antagonist (LAMA) Fixed-dose combination (FDC), and 8,163 patients were treated with inhaled corticosteroids (ICSs)/ LABA FDC
Our results suggest that ICS/LAMA/LABA FDC was more effective in reducing all-cause mortality than LABA/ LAMA FDC and more effective in reducing the risk of moderate or severe COPD exacerbation and prolonging the time to first exacerbation than ICS/LABA or LABA/ LAMA FDC

Summary

Introduction

In some RCTs comparing triple therapy with dual therapy in COPD, there might be a bias resulting from the use of multiple inhaler devices This meta-analysis included only RCTs that compared ICS/LABA/LAMA vs LABA/LAMA or ICS/LABA using a single device. The Global Initiative for Obstructive Lung Disease (GOLD) management strategy recommends using ICS/ LABA + LAMA in patients with persistent breathlessness, exercise limitation or persistent exacerbation, but it does not specify when to use single-inhaler triple therapy [4]. Single-inhaler therapy has been shown to improve lung function and health status [8, 9], but evidence of a reduction in mortality with single-inhaler triple therapy versus single-inhaler dual therapy has not been well documented in previous meta-analyses

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Results

Conclusion