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Review
, 2011 (12), CD007033

Inhaled Corticosteroids Versus Long-Acting beta(2)-agonists for Chronic Obstructive Pulmonary Disease

Affiliations
Review

Inhaled Corticosteroids Versus Long-Acting beta(2)-agonists for Chronic Obstructive Pulmonary Disease

Sally Spencer et al. Cochrane Database Syst Rev.

Abstract

Background: Long-acting beta(2)-agonists and inhaled corticosteroids can be used as maintenance therapy by patients with moderate to severe chronic obstructive pulmonary disease. These interventions are often taken together in a combination inhaler. However, the relative added value of the two individual components is unclear.

Objectives: To determine the relative effects of inhaled corticosteroids (ICS) compared to long-acting beta(2)-agonists (LABA) on clinical outcomes in patients with stable chronic obstructive pulmonary disease.

Search methods: We searched the Cochrane Airways Group Specialised Register of trials (latest search August 2011) and reference lists of articles.

Selection criteria: We included randomised controlled trials comparing inhaled corticosteroids and long-acting beta(2)-agonists in the treatment of patients with stable chronic obstructive pulmonary disease.

Data collection and analysis: Three authors independently assessed trials for inclusion and then extracted data on trial quality, study outcomes and adverse events. We also contacted study authors for additional information.

Main results: We identified seven randomised trials (5997 participants) of good quality with a duration of six months to three years. All of the trials compared ICS/LABA combination inhalers with LABA and ICS as individual components. Four of these trials included fluticasone and salmeterol monocomponents and the remaining three included budesonide and formoterol monocomponents. There was no statistically significant difference in our primary outcome, the number of patients experiencing exacerbations (odds ratio (OR) 1.22; 95% CI 0.89 to 1.67), or the rate of exacerbations per patient year (rate ratio (RR) 0.96; 95% CI 0.89 to 1.02) between inhaled corticosteroids and long-acting beta(2)-agonists. The incidence of pneumonia, our co-primary outcome, was significantly higher among patients on inhaled corticosteroids than on long-acting beta(2)-agonists whether classified as an adverse event (OR 1.38; 95% CI 1.10 to 1.73) or serious adverse event (Peto OR 1.48; 95% CI 1.13 to 1.93). Results of the secondary outcomes analysis were as follows. Mortality was higher in patients on inhaled corticosteroids compared to patients on long-acting beta(2)-agonists (Peto OR 1.17; 95% CI 0.97 to 1.42), although the difference was not statistically significant. Patients treated with beta(2)-agonists showed greater improvements in pre-bronchodilator FEV(1) compared to those treated with inhaled corticosteroids (mean difference (MD) 18.99 mL; 95% CI 0.52 to 37.46), whilst greater improvements in health-related quality of life were observed in patients receiving inhaled corticosteroids compared to those receiving long-acting beta(2)-agonists (St George's Respiratory Questionnaire (SGRQ) MD -0.74; 95% CI -1.42 to -0.06). In both cases the differences were statistically significant but rather small in magnitude. There were no statistically significant differences between ICS and LABA in the number of hospitalisations due to exacerbations, number of mild exacerbations, peak expiratory flow, dyspnoea, symptoms scores, use of rescue medication, adverse events, all cause hospitalisations, or withdrawals from studies.

Authors' conclusions: Placebo-controlled trials have established the benefits of both long-acting beta-agonist and inhaled corticosteroid therapy for COPD patients as individual therapies. This review, which included trials allowing comparisons between LABA and ICS, has shown that the two therapies confer similar benefits across the majority of outcomes, including the frequency of exacerbations and mortality. Use of long-acting beta-agonists appears to confer a small additional benefit in terms of improvements in lung function compared to inhaled corticosteroids. On the other hand, inhaled corticosteroid therapy shows a small advantage over long-acting beta-agonist therapy in terms of health-related quality of life, but inhaled corticosteroids also increase the risk of pneumonia. This review supports current guidelines advocating long-acting beta-agonists as frontline therapy for COPD, with regular inhaled corticosteroid therapy as an adjunct in patients experiencing frequent exacerbations.

Conflict of interest statement

Sally Spencer has had consultancy arrangements with GlaxoSmithKline who make long‐acting beta2‐agonists and inhaled corticosteroids. She has also previously been funded by GlaxoSmithKline. David Evans, Christopher Cates and Charlotta Karner do not have any known conflicts of interest.

Figures

Figure 1
Figure 1
Risk of bias summary: review authors' judgements about each 'Risk of bias' item for each included study.
Figure 2
Figure 2
Forest plot of comparison: 1 Inhaled corticosteroids versus long‐acting beta2‐agonists by ICS and LABA, outcome: 1.1 Exacerbation rate ratios.
Figure 3
Figure 3
Forest plot of comparison: 2 Inhaled corticosteroids versus long‐acting beta2‐agonists by length of study, outcome: 2.1 Exacerbation rate ratios.
Figure 4
Figure 4
Forest plot of comparison: 1 Inhaled corticosteroids versus long‐acting beta2‐agonists by ICS and LABA, outcome: 1.4 Pneumonia adverse event.
Figure 5
Figure 5
On LABA 7 people out of 100 had pneumonia (adverse event) over 2.4 years, compared to 9 (95% CI 8 to 12) out of 100 for the ICS group. The NNT(H) for one extra person to suffer pneumonia on ICS was 42 (95% CI: 155 to 23).
Figure 6
Figure 6
Forest plot of comparison: 1 Inhaled corticosteroids versus long‐acting beta2‐agonists by ICS and LABA, outcome: 1.5 Pneumonia serious adverse event.
Analysis 1.1
Analysis 1.1
Comparison 1 Inhaled corticosteroids (ICS) versus long‐acting beta2‐agonists (LABA) by ICS and LABA, Outcome 1 Exacerbation rate ratios.
Analysis 1.2
Analysis 1.2
Comparison 1 Inhaled corticosteroids (ICS) versus long‐acting beta2‐agonists (LABA) by ICS and LABA, Outcome 2 Exacerbations.
Analysis 1.3
Analysis 1.3
Comparison 1 Inhaled corticosteroids (ICS) versus long‐acting beta2‐agonists (LABA) by ICS and LABA, Outcome 3 Hospitalisations due to exacerbations.
Analysis 1.4
Analysis 1.4
Comparison 1 Inhaled corticosteroids (ICS) versus long‐acting beta2‐agonists (LABA) by ICS and LABA, Outcome 4 Pneumonia adverse event.
Analysis 1.5
Analysis 1.5
Comparison 1 Inhaled corticosteroids (ICS) versus long‐acting beta2‐agonists (LABA) by ICS and LABA, Outcome 5 Pneumonia serious adverse event.
Analysis 1.6
Analysis 1.6
Comparison 1 Inhaled corticosteroids (ICS) versus long‐acting beta2‐agonists (LABA) by ICS and LABA, Outcome 6 Pre‐dose FEV1.
Analysis 1.7
Analysis 1.7
Comparison 1 Inhaled corticosteroids (ICS) versus long‐acting beta2‐agonists (LABA) by ICS and LABA, Outcome 7 Post‐dose FEV1.
Analysis 1.8
Analysis 1.8
Comparison 1 Inhaled corticosteroids (ICS) versus long‐acting beta2‐agonists (LABA) by ICS and LABA, Outcome 8 Mild exacerbations.
Analysis 1.9
Analysis 1.9
Comparison 1 Inhaled corticosteroids (ICS) versus long‐acting beta2‐agonists (LABA) by ICS and LABA, Outcome 9 Mortality.
Analysis 1.10
Analysis 1.10
Comparison 1 Inhaled corticosteroids (ICS) versus long‐acting beta2‐agonists (LABA) by ICS and LABA, Outcome 10 Health‐related quality of life SGRQ.
Analysis 1.11
Analysis 1.11
Comparison 1 Inhaled corticosteroids (ICS) versus long‐acting beta2‐agonists (LABA) by ICS and LABA, Outcome 11 Dyspnoea symptom score 0‐4.
Analysis 1.12
Analysis 1.12
Comparison 1 Inhaled corticosteroids (ICS) versus long‐acting beta2‐agonists (LABA) by ICS and LABA, Outcome 12 Dyspnoea TDI.
Analysis 1.13
Analysis 1.13
Comparison 1 Inhaled corticosteroids (ICS) versus long‐acting beta2‐agonists (LABA) by ICS and LABA, Outcome 13 Symptoms.
Analysis 1.14
Analysis 1.14
Comparison 1 Inhaled corticosteroids (ICS) versus long‐acting beta2‐agonists (LABA) by ICS and LABA, Outcome 14 Adverse events.
Analysis 1.15
Analysis 1.15
Comparison 1 Inhaled corticosteroids (ICS) versus long‐acting beta2‐agonists (LABA) by ICS and LABA, Outcome 15 Serious adverse events (non‐fatal).
Analysis 1.16
Analysis 1.16
Comparison 1 Inhaled corticosteroids (ICS) versus long‐acting beta2‐agonists (LABA) by ICS and LABA, Outcome 16 Withdrawals.
Analysis 2.1
Analysis 2.1
Comparison 2 Inhaled corticosteroids versus long‐acting beta2‐agonists by length of study, Outcome 1 Exacerbation rate ratios.
Analysis 2.2
Analysis 2.2
Comparison 2 Inhaled corticosteroids versus long‐acting beta2‐agonists by length of study, Outcome 2 Pneumonia serious adverse event.

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