Addition of long-acting beta2-agonists to inhaled steroids versus higher dose inhaled steroids in adults and children with persistent asthma

Abstract

Background In asthmatic patients inadequately controlled on inhaled corticosteroids and/or those with moderate persistent asthma, two main options are recommended: the combination of a long-acting inhaled ß2 agonist (LABA) with inhaled corticosteroids (ICS) or use of a higher dose of inhaled corticosteroids. Objectives To determine the effect of the combination of long-acting ß2 agonists and inhaled corticosteroids compared to a higher dose of inhaled corticosteroids on the risk of asthma exacerbations, pulmonary function and on other measures of asthma control, and to look for characteristics associated with greater benefit for either treatment option. Search methods We identified randomised controlled trials (RCTs) through electronic database searches (MEDLINE, EMBASE and CINAHL), bibliographies of RCTs, clinical trial registries and correspondence with manufacturers until May 2008. Selection criteria RCTs that compared the combination of inhaled LABA and ICS to a higher dose of inhaled corticosteroids, in children and adults with asthma. Data collection and analysis Two authors independently assessed methodological quality and extracted data. We obtained confirmation from the trialists when possible. The primary endpoint was the number of patients experiencing one or more asthma exacerbations requiring oral corticosteroids. Main results This review included 48 studies (15,155 participants including 1155 children and 14,000 adults). Participants were inadequately controlled on their current ICS regimen, experiencing ongoing symptoms and with generally moderate (FEV1 60% to 79% of predicted) airway obstruction. The studies tested the combination of salmeterol or formoterol with a median dose of 400 mcg/day of beclomethasone or equivalent (BDP-eq) compared to a median of 1000 mcg/day of BDP-eq, usually for 24 weeks or less. There was a statistically significantly lower risk of exacerbations requiring systemic corticosteroids in patients treated with LABA and ICS (RR 0.88, 95% CI 0.78 to 0.98, 27 studies, N = 10,578) from 11.45% to 10%, with a number needed to treat of 73 (median study duration: 12 weeks). The study results were dominated by adult studies; trial data from three paediatric studies showed a trend towards increased risk of rescue oral steroids (RR 1.24, 95% CI 0.58 to 2.66) and hospital admission (RR 2.21, 95% CI 0.74 to 6.64) associated with combination therapy. Overall, there was no statistically significant difference in the risk ratios for either hospital admission (RR 1.02, 95% CI 0.67 to 1.56) or serious adverse events (RR 1.12, 95% CI 0.91 to 1.37). The combination of LABA and ICS resulted in significantly greater but modest improvement from baseline in lung function, symptoms and rescue medication use than with higher ICS dose. Despite no significant group difference in the risk of overall adverse events (RR 0.99, 95% CI 0.95 to 1.03), there was an increase in the risk of tremor (RR 1.84, 95% CI 1.20 to 2.82) and a lower risk of oral thrush (RR 0.58, 95% CI 0.40 to 0.86)) in the LA...

Real-life effectiveness of budesonide/formoterol maintenance and reliever therapy in asthma patients across Asia: SMARTASIA study

“…Further improvement of symptoms and lung function may be attributed to the SMART regimen. In addition, the improvements in symptom control, lung function, and reduction in as-needed reliever medications were comparable to those previously reported in earlier studies [24,27]. …”

Real-life effectiveness of budesonide/formoterol maintenance and reliever therapy in asthma patients across Asia: SMARTASIA study

“…Further improvement of symptoms and lung function may be attributed to the SMART regimen. In addition, the improvements in symptom control, lung function, and reduction in as-needed reliever medications were comparable to those previously reported in earlier studies [24,27]. …”

Long-acting beta2 agonists for childhood asthma

“…2,4 These observations are consistent with a recent metaanalysis which found an increased risk of severe and life-threatening asthma exacerbations associated with long-acting beta 2 agonists, even when they were used with concomitant inhaled corticosteroids. 6 This finding contradicts previous suggestions that the increased risk of severe exacerbations with long-acting beta 2 agonists is only seen in patients treated with longacting beta 2 agonists alone.…”

Long-Term Fluticasone Propionate/Formoterol Fumarate Combination Therapy Is Associated with a Low Incidence of Severe Asthma Exacerbations

“…The pooled incidence of OCS exacerbations for the ICS and LABA combinations in the three studies from Chauhan and Ducharme's Cochrane review ( 33 ) was very similar to that from the Ducharme et al, ( 22 ) at 16.7% (95% CI: 14.9, 18.5, n/N = 275/1643, Table 4 ). OCS exacerbation rates were more than 2-fold higher in the study by Price et al (36.3%, Fig.…”

Real-life effectiveness of budesonide/formoterol maintenance and reliever therapy in asthma patients across Asia: SMARTASIA study

“…Further improvement of symptoms and lung function may be attributed to the SMART regimen. In addition, the improvements in symptom control, lung function, and reduction in as-needed reliever medications were comparable to those previously reported in earlier studies [24,27]. …”

Long-acting beta2 agonists for childhood asthma

“…2,4 These observations are consistent with a recent metaanalysis which found an increased risk of severe and life-threatening asthma exacerbations associated with long-acting beta 2 agonists, even when they were used with concomitant inhaled corticosteroids. 6 This finding contradicts previous suggestions that the increased risk of severe exacerbations with long-acting beta 2 agonists is only seen in patients treated with longacting beta 2 agonists alone.…”

Long-Term Fluticasone Propionate/Formoterol Fumarate Combination Therapy Is Associated with a Low Incidence of Severe Asthma Exacerbations

“…The pooled incidence of OCS exacerbations for the ICS and LABA combinations in the three studies from Chauhan and Ducharme's Cochrane review ( 33 ) was very similar to that from the Ducharme et al, ( 22 ) at 16.7% (95% CI: 14.9, 18.5, n/N = 275/1643, Table 4 ). OCS exacerbation rates were more than 2-fold higher in the study by Price et al (36.3%, Fig.…”

Real-life effectiveness of budesonide/formoterol maintenance and reliever therapy in asthma patients across Asia: SMARTASIA study

“…Further improvement of symptoms and lung function may be attributed to the SMART regimen. In addition, the improvements in symptom control, lung function, and reduction in as-needed reliever medications were comparable to those previously reported in earlier studies [24,27]. …”

Long-acting beta2 agonists for childhood asthma

“…2,4 These observations are consistent with a recent metaanalysis which found an increased risk of severe and life-threatening asthma exacerbations associated with long-acting beta 2 agonists, even when they were used with concomitant inhaled corticosteroids. 6 This finding contradicts previous suggestions that the increased risk of severe exacerbations with long-acting beta 2 agonists is only seen in patients treated with longacting beta 2 agonists alone.…”

Long-Term Fluticasone Propionate/Formoterol Fumarate Combination Therapy Is Associated with a Low Incidence of Severe Asthma Exacerbations

“…The pooled incidence of OCS exacerbations for the ICS and LABA combinations in the three studies from Chauhan and Ducharme's Cochrane review ( 33 ) was very similar to that from the Ducharme et al, ( 22 ) at 16.7% (95% CI: 14.9, 18.5, n/N = 275/1643, Table 4 ). OCS exacerbation rates were more than 2-fold higher in the study by Price et al (36.3%, Fig.…”