Comparing inhaled corticosteroids with long-acting beta2-agonists in treating chronic obstructive pulmonary disease (COPD)

Inhalers containing corticosteroids, long-acting beta2-agonists or both can be used to treat severe chronic obstructive pulmonary disease (COPD). However, the benefits and harms of the two individual treatments are unclear when comparing one treatment with the other.

We looked at clinical trials that compared the two kinds of inhalers to find the effects of each on health and well-being in patients with COPD. We found seven studies (involving 5997 participants) comparing the long-term benefits and side effects of inhaled corticosteroids and long-acting beta2-agonists for treating COPD. Overall, we found no significant difference between the two drugs in the number of people having an exacerbation (worsening of COPD symptoms). More people taking inhaled corticosteroids suffered episodes of pneumonia compared to people using long-acting beta2-agonists, although  pneumonia was extremely rare in both groups. Inhaled corticosteroids do not improve lung function as much as long-acting beta2-agonists but did improve patients' quality of life more than long-acting beta2-agonists. The differences in lung function and quality of life were rather small.

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.

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Background: 

Long-acting beta2-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 beta2-agonists (LABA) on clinical outcomes in patients with stable chronic obstructive pulmonary disease.

Search strategy: 

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 beta2-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 beta2-agonists. The incidence of pneumonia, our co-primary outcome, was significantly higher among patients on inhaled corticosteroids than on long-acting beta2-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 beta2-agonists (Peto OR 1.17; 95% CI 0.97 to 1.42), although the difference was not statistically significant. Patients treated with beta2-agonists showed greater improvements in pre-bronchodilator FEV1 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 beta2-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.

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