Triple vs Dual Inhaler Therapy and Asthma Outcomes in Moderate to Severe Asthma: A Systematic Review and Meta-analysis

An RCT comparing dual vs. triple medication inhaler therapy for chronic treatment of people with moderate to severe asthma. (a 5% reduction in severe exacerbations but no improvement in QOL) James W. Mold, MD. MPH

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Importance: The benefits and harms of adding long-acting muscarinic antagonists (LAMAs) to inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs) for moderate to severe asthma remain unclear.

Objective: To systematically synthesize the outcomes and adverse events associated with triple therapy (ICS, LABA, and LAMA) vs dual therapy (ICS plus LABA) in children and adults with persistent uncontrolled asthma.

Data sources: MEDLINE, Embase, CENTRAL, ICTRP, FDA, and EMA databases from November 2017, to December 8, 2020, without language restriction.

Study selection: Two investigators independently selected randomized clinical trials (RCTs) comparing triple vs dual therapy in patients with moderate to severe asthma.

Data extraction and synthesis: Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses, including individual patient-level exacerbation data, were used. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess certainty (quality) of the evidence.

Main outcomes and measures: Severe exacerbations, asthma control (measured using the Asthma Control Questionnaire [ACQ-7], a 7-item list with each item ranging from 0 [totally controlled] to 6 [severely uncontrolled]; minimal important difference, 0.5), quality of life (measured using the Asthma-related Quality of Life [AQLQ] tool; score range, 1 [severely impaired] to 7 [no impairment]; minimal important difference, 0.5), mortality, and adverse events.

Results: Twenty RCTs using 3 LAMA types that enrolled 11 894 children and adults (mean age, 52 years [range, 9-71 years]; 57.7% female) were included. High-certainty evidence showed that triple therapy vs dual therapy was significantly associated with a reduction in severe exacerbation risk (9 trials [9932 patients]; 22.7% vs 27.4%; risk ratio, 0.83 [95% CI, 0.77 to 0.90]) and an improvement in asthma control (14 trials [11 230 patients]; standardized mean difference [SMD], -0.06 [95% CI, -0.10 to -0.02]; mean difference in ACQ-7 scale, -0.04 [95% CI, -0.07 to -0.01]). There were no significant differences in asthma-related quality of life (7 trials [5247 patients]; SMD, 0.05 [95% CI, -0.03 to 0.13]; mean difference in AQLQ score, 0.05 [95% CI, -0.03 to 0.13]; moderate-certainty evidence) or mortality (17 trials [11 595 patients]; 0.12% vs 0.12%; risk ratio, 0.96 [95% CI, 0.33 to 2.75]; high-certainty evidence) between dual and triple therapy. Triple therapy was significantly associated with increased dry mouth and dysphonia (10 trials [7395 patients]; 3.0% vs 1.8%; risk ratio, 1.65 [95% CI, 1.14 to 2.38]; high-certainty evidence), but treatment-related and serious adverse events were not significantly different between groups (moderate-certainty evidence).

Conclusions and relevance: Among children (aged 6 to 18 years) and adults with moderate to severe asthma, triple therapy, compared with dual therapy, was significantly associated with fewer severe asthma exacerbations and modest improvements in asthma control without significant differences in quality of life or mortality.

Author/s:

Kim, L.H.Y., Saleh, C., Whalen-Browne, A., O'Byrne, P.M., Chu, D.K.

Inhaler Technique Education and Exacerbation Risk in Older Adults with Asthma or Chronic Obstructive Pulmonary Disease: A Meta-Analysis

Tracy Ashby — Tue, 30 Oct 2018 05:00:00 +0000

Date Added:

October 30, 2018

Journal/Publication:

Journal of the American Geriatrics Society

Publisher:

John Wiley & Sons, Inc.

Publication Date:

October 6, 2018

URL:

Inhaler Technique Education and Exacerbation Risk in Older Adults with Asthma or Chronic Obstructive Pulmonary Disease: A Meta‐Analysis

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1111/jgs.15602

Keywords

chronic obstructive pulmonary disease

MeSH

pulmonary disease, chronic obstructive

nebulizers and vaporizers

asthma

This meta-analysis, focused on COPD patients, is a reminder of the importance of training patients to use their inhalers properly. That suggests that practices have at least one inhaler trainer and placebo inhalers or that patients requiring inhalers should be referred to a respiratory therapist or pharmacist for training.

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Objectives

To evaluate the effect of inhaler education programs on clinical outcomes and exacerbation rates in older adults with asthma or chronic obstructive pulmonary disease (COPD).

Design

Systematic review and meta‐analysis.

Setting and Participants

Older adults with asthma or COPD, either in primary or secondary health care and pharmacy setting.

Measurements

We searched the Medline, Embase, and Central databases according to the main eligibility criteria for inclusion: systematic reviews, meta‐analysis, clinical trials and quasi‐experimental studies; participants aged 65 and older; education on inhaler technique and reporting of disease control and exacerbation rates. We used the Grading of Recommendations, Assessment, Development and Evaluations scale for quality assessment and used a random‐effect model with Mantel–Haenszel adjustment to perform a meta‐analysis.

Results

We included 8 studies (4 randomized, 4 quasi‐experimental) with a total of 1,812 participants. The most frequent type of intervention was physical demonstration of inhaler technique, training with placebo devices. Five studies showed significant reduction in exacerbation rates (pooled risk ratio=0.71, 95% confidence interval=0.59–0.86; p < .001), although effect on disease control and quality of life showed high discrepancy in the reported results, and all randomized studies revealed uncertainty in their risk of bias assessment.

Conclusion

All interventions seemed to improve inhaler performance and clinically relevant outcomes, but a placebo device could be the most effective. There is evidence that interventions reduce exacerbation risk in older adults, although to an overall moderate degree.

Author/s:

Maricoto, Tiago, Monteiro, Luís, Gama, Jorge M. R., Correia-de-Sousa, Jamie, Taborda-Barata, Luís