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. 2021 Jan 25;7(1):00701-2020.
doi: 10.1183/23120541.00701-2020. eCollection 2021 Jan.

ICS-formoterol reliever versus ICS and short-acting β2-agonist reliever in asthma: a systematic review and meta-analysis

Lee Hatter  1   2 , Pepa Bruce  1 , Irene Braithwaite  1 , Mark Holliday  1 , James Fingleton  1   3 , Mark Weatherall  3   4 , Richard Beasley  1   3
Affiliations

ICS-formoterol reliever versus ICS and short-acting β2-agonist reliever in asthma: a systematic review and meta-analysis

Lee Hatter et al. ERJ Open Res. .

Abstract

Background: The Global Initiative for Asthma recommends as-needed inhaled corticosteroid (ICS)-formoterol as an alternative to maintenance ICS plus short-acting β2-agonist (SABA) reliever at step 2 of its stepwise treatment algorithm. Our aim was to assess the efficacy and safety of these two treatment regimens, with a focus on prevention of severe exacerbation.

Methods: We performed a systematic review and meta-analysis of all randomised controlled trials (RCTs) comparing as-needed ICS-formoterol with maintenance ICS plus SABA. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrials.gov were searched from database inception to 12 December 2019. The primary outcome was time to first severe exacerbation. RCTs were excluded if they used as-needed budesonide-formoterol as part of a maintenance and reliever regimen, or did not report on severe exacerbations. The review is registered with PROSPERO (identifier number CRD42020154680).

Results: Four RCTs (n=8065 participants) were included in the analysis. As-needed ICS-formoterol was associated with a prolonged time to first severe exacerbation (hazard ratio 0.85, 95% CI 0.73-1.00; p=0.048) and reduced daily ICS dose (mean difference -177.3 μg, 95% CI -182.2--172.4 μg). Asthma symptom control was worse in the as-needed group (Asthma Control Questionnaire-5 mean difference 0.12, 95% CI 0.09-0.14), although this did not meet the minimal clinically important difference of 0.50 units. There was no significant difference in serious adverse events (OR 1.07, 95% CI 0.84-1.36).

Conclusion: As-needed ICS-formoterol offers a therapeutic alternative to maintenance low-dose ICS plus SABA in asthma and may be the preferred option when prevention of severe exacerbation is the primary aim of treatment.

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Conflict of interest statement

Conflict of interest: L. Hatter has nothing to disclose. Conflict of interest: P. Bruce has nothing to disclose. Conflict of interest: I. Braithwaite reports personal fees from Equillium outside the submitted work. Conflict of interest: M. Holliday reports grants from AstraZeneca and the Health Research Council of New Zealand outside the submitted work. Conflict of interest: J. Fingleton reports grants, personal fees and nonfinancial support from AstraZeneca; grants from Genentech; grants, personal fees and nonfinancial support from GlaxoSmithKline; and personal fees and nonfinancial support from Boehringer lngleheim, all outside the submitted work. Conflict of interest: M. Weatherall has nothing to disclose. Conflict of interest: R. Beasley reports grants and personal fees from AstraZeneca, grants from Genentech and GlaxoSmithKline, and personal fees from Theravance and Avillion, outside the submitted work.

Figures

FIGURE 1
FIGURE 1
Flow diagram of literature search and screening process. ICS: inhaled corticosteroid; LABA: long-acting β2-agonist; RCT: randomised controlled trial.
FIGURE 2
FIGURE 2
Pooled fixed effect for the hazard ratio of time to first severe exacerbation.
FIGURE 3
FIGURE 3
Pooled fixed effect of a) rate ratio (RR) of severe exacerbations, and b) odds ratio for relative risk of severe exacerbations.
FIGURE 4
FIGURE 4
Pooled fixed effect of the combination of emergency department visits or hospitalisations. POR: Peto odds ratio.
See this image and copyright information in PMC

References

    1. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention 2020. Available from: http://ginasthma.com Date last accessed: May 6, 2020.
    1. O'Byrne PM, FitzGerald JM, Bateman ED, et al. . Inhaled combined budesonide-formoterol as needed in mild asthma. N Engl J Med 2018; 378: 1865–1876. doi:10.1056/NEJMoa1715274 - DOI - PubMed
    1. Beasley R, Holliday M, Reddel HK, et al. . Controlled trial of budesonide-formoterol as needed for mild asthma. N Engl J Med 2019; 380: 2020–2030. doi:10.1056/NEJMoa1901963 - DOI - PubMed
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