Addition of inhaled long-acting beta2-agonists to inhaled steroids as first line therapy for persistent asthma in steroid-naive adults

Ni Chroinin M, Greenstone IR, Ducharme FM

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Summary

In patients who have inadequate asthma control and require daily anti-inflammatory therapy, there is insufficient evidence to support initiating therapy with a combination of inhaled glucocorticoids and long-acting beta2-agonist - rather than inhaled glucocorticoids alone.

Most consensus statements recommend the addition of long-acting beta2-agonists - as second line therapy in asthmatic individuals who are insufficiently controlled on inhaled glucocorticoids. The purpose of this review was to compare the benefit and safety profile of initiating treatment with a combination of inhaled glucocorticoids and long-acting beta2-agonists - as compared to inhaled glucocorticoids alone in asthmatic patients who had not received a prior trial of inhaled corticosteroids alone. This review analysed randomised controlled trials in which children and adults with asthma had not received inhaled corticosteroids for one month or more (steroid naïve). We compared the outcome of those who started asthma therapy with inhaled glucocorticoids alone versus those who received a combination of inhaled glucocorticoids and long-acting beta2-agonists. As of April 2004, 18 trials (all pertaining to adults) addressed this question: nine trials contributed enough data to be analysed. The combination therapy provided no significantly increased protection against exacerbations but provided a greater improvement in lung function and in symptoms.

This is a Cochrane review abstract and plain language summary, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2008 Issue 3, Copyright © 2008 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).
This record should be cited as: Ni Chroinin M, Greenstone IR, Ducharme FM. Addition of inhaled long-acting beta2-agonists to inhaled steroids as first line therapy for persistent asthma in steroid-naive adults. Cochrane Database of Systematic Reviews 2005, Issue 2. Art. No.: CD005307. DOI: 10.1002/14651858.CD005307

This version first published online: April 20. 2005

Abstract

Background

Consensus statements recommend the addition of long-acting inhaled beta2-agonists only in asthmatic patients who are inadequately controlled on inhaled corticosteroids.

Objectives

To compare the efficacy of initiating anti-inflammatory therapy using the combination of inhaled corticosteroids and long-acting beta2-agonists (ICS+LABA) as compared to inhaled corticosteroids alone (ICS alone) in steroid-naive children and adults with persistent asthma.

Search strategy

We identified randomised controlled trials (RCTs) through electronic database searches (Cochrane Airways Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and CINAHL) until April 2004, bibliographies of identified RCTs and correspondence with manufacturers.

Selection criteria

RCTs comparing the combination of inhaled corticosteroids and long-acting beta2-agonists (ICS + LABA) to inhaled corticosteroids (ICS) alone in steroid-naive children and adults with asthma.

Data collection and analysis

Studies were assessed independently by each reviewer for methodological quality and data extraction. Confirmation was obtained from the trialists when possible. The primary endpoint was rate of asthma exacerbations requiring systemic corticosteroids. Secondary endpoints included pulmonary function tests (PFTs), symptoms, use of other measures of asthma control, adverse events, and withdrawal rates.

Main results

Eighteen trials met the inclusion criteria; nine (totaling 1061 adults) contributed sufficient data to be analysed. Baseline forced expiratory volume in one minute (FEV1) was less than 80% predicted value in four trials and equal to or greater than 80% in five trials. The long-acting beta2-agonists (LABA) formoterol (N=2) or salmeterol (N=7) were added to a dose of at least 800 µg/day of beclomethasone dipropionate (BDP) equivalent of inhaled corticosteroids (ICS) in three trials and to at least 400 µg/day in the six remaining trials. Treatment with ICS plus LABA was not associated with a lower risk of exacerbations requiring oral corticosteroids than ICS alone (relative risk (RR) 1.2; 95% confidence interval (CI) 0.8 to 1.9). FEV1 improved significantly with LABA (weighted mean difference (WMD) 210 ml; 95% CI 120 to 300), as did symptom-free days (WMD 10.74%; 95% CI 1.86 to 19.62), but the change in use of rescue fast-acting beta2-agonists was not significantly different between the groups (WMD -0.4 puff/day, 95% CI -0.9 to 0.1). There was no significant group difference in adverse events (RR 1.1; 95% CI 0.8 to 1.5), withdrawals (RR 0.9; 95% CI 0.6 to 1.2), or withdrawals due to poor asthma control (RR 1.3; 95% CI 0.5 to 3.4).

Authors' conclusions

In steroid-naive patients with mild to moderate airway obstruction, the initiation of inhaled corticosteroids in combination with long-acting beta2-agonists does not significantly reduce the rate of exacerbations over that achieved with inhaled corticosteroids alone; it does improve lung function and symptom-free days but does not reduce rescue beta2-agonist use as compared to inhaled steroids alone. Both options appear safe. There is insufficient evidence at present to recommend use of combination therapy rather than ICS alone as a first-line treatment.

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