Article

Addition to inhaled corticosteroids of long-acting beta2-agonists versus anti-leukotrienes for chronic asthma.

Cochrane database of systematic reviews (Online) (Impact Factor: 5.94). 01/2014; 1:CD003137. DOI: 10.1002/14651858.CD003137.pub5
Source: PubMed

ABSTRACT Asthma patients who continue to experience symptoms despite taking regular inhaled corticosteroids (ICS) represent a management challenge. Long-acting beta2-agonists (LABA) and anti-leukotrienes (LTRA) are two treatment options that could be considered as add-on therapy to ICS.
To compare the safety and efficacy of adding LABA versus LTRA to the treatment regimen for children and adults with asthma who remain symptomatic in spite of regular treatment with ICS. We specifically wished to examine the relative impact of the two agents on asthma exacerbations, lung function, symptoms, quality of life, adverse health events and withdrawals.
We searched the Cochrane Airways Group Specialised Register until December 2012. We consulted reference lists of all included studies and contacted pharmaceutical manufacturers to ask about other published or unpublished studies.
We included randomised controlled trials (RCTs) conducted in adults or children with recurrent asthma that was treated with ICS along with a fixed dose of a LABA or an LTRA for a minimum of four weeks.
Two review authors independently assessed the risk of bias of included studies and extracted data. We sought unpublished data and further details of study design when necessary.
We included 18 RCTs (7208 participants), of which 16 recruited adults and adolescents (6872) and two recruited children six to 17 years of age (336) with asthma and significant reversibility to bronchodilator at baseline. Fourteen (79%) trials were of high methodological quality.The risk of exacerbations requiring systemic corticosteroids (primary outcome of the review) was significantly lower with the combination of LABA + ICS compared with LTRA + ICS-from 13% to 11% (eight studies, 5923 adults and 334 children; risk ratio (RR) 0.87, 95% confidence interval (CI) 0.76 to 0.99; high-quality evidence). The number needed to treat for an additional beneficial outcome (NNTB) with LABA compared with LTRA to prevent one additional exacerbation over four to 102 weeks was 62 (95% CI 34 to 794). The choice of LTRA, the dose of ICS and the participants' age group did not significantly influence the magnitude of effect. Although results were inconclusive, the effect appeared stronger in trials that used a single device rather than two devices to administer ICS and LABA and in trials of less than 12 weeks' duration.The addition of LABA to ICS was associated with a statistically greater improvement from baseline in lung function, as well as in symptoms, rescue medication use and quality of life, although the latter effects were modest. LTRA was superior in the prevention of exercise-induced bronchospasm. More participants were satisfied with the combination of LABA + ICS than LTRA + ICS (three studies, 1625 adults; RR 1.12, 95% CI 1.04 to 1.20; moderate-quality evidence). The overall risk of withdrawal was significantly lower with LABA + ICS than with LTRA + ICS (13 studies, 6652 adults and 308 children; RR 0.84, 95% CI 0.74 to 0.96; moderate-quality evidence). Although the risk of overall adverse events was equivalent between the two groups, the risk of serious adverse events (SAE) approached statistical significance in disfavour of LABA compared with LTRA (nine studies, 5658 adults and 630 children; RR 1.33, 95% CI 0.99 to 1.79; P value 0.06; moderate-quality evidence), with no apparent impact of participants' age group.The following adverse events were reported, but no significant differences were demonstrated between groups: headache (11 studies, N = 6538); cardiovascular events (five studies, N = 5163), osteopenia and osteoporosis (two studies, N = 2963), adverse events (10 studies, N = 5977 adults and 300 children). A significant difference in the risk of oral moniliasis was noted, but this represents a low occurrence rate.
In adults with asthma that is inadequately controlled by predominantly low-dose ICS with significant bronchodilator reversibility, the addition of LABA to ICS is modestly superior to the addition of LTRA in reducing oral corticosteroid-treated exacerbations, with an absolute reduction of two percentage points. Differences favouring LABA over LTRA as adjunct therapy were observed in lung function and, to a lesser extend, in rescue medication use, symptoms and quality of life. The lower overall withdrawal rate and the higher proportion of participants satisfied with their therapy indirectly favour the combination of LABA + ICS over LTRA + ICS. Evidence showed a slightly increased risk of SAE with LABA compared with LTRA, with an absolute increase of one percentage point. Our findings modestly support the use of a single inhaler for the delivery of both LABA and low- or medium-dose ICS. Because of the paucity of paediatric trials, we are unable to draw firm conclusions about the best adjunct therapy in children.

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    ABSTRACT: Abstract Objective: To summarize the principal findings pertaining to most effective long term pharmacologic treatment of childhood asthma. Methods: Systematic reviews of randomized clinical trials (SRCTs) on pharmacologic chronic treatment in children (1 to 18 years) with persistent asthma were retrieved through MEDLINE, EMBASE, CINAHL, SCOPUS and CDSR (up to January2014). Results: One hundred eighty-three SRCTs were searched from databases. Among those, 39 SRCTs were included: 2 were related to step 1, 24 to step 2, 9 to step 3-4, and 4 to step 5 (according with NAEPP and GINA guidelines). The methodological quality of these SRCTs was determined using the AMSTAR tool. Results: For Step 1: Addition of ipatropium bromide to short-acting beta2-agonists does not show any benefit. For Step 2: In preschoolers, inhaled corticosteroids (ICS) reduce severe exacerbations and improve other clinical and lung function parameters. In children, ICS are superior to leukotriene receptor antagonist (LTRA), cromones, or xantines in reducing severe exacerbations, improving lung function and other clinical outcomes. Fluticasone propionate (FP) is better than beclomethasone dipropionate (BDP) or budesonide only for lung function; but similar to hydrofluoroalkane-BDP or to ciclosenide. Compared to low ICSs doses, moderate doses result in only better lung function, but this is not true for FP. For step 3-4: Adding LTRA to ICS confers a small benefit; adding LABA improves lung function but does not reduce exacerbations more than double or higher ICSs doses. For step 5: Adding omalizumab decreases exacerbations. Conclusions: SRCTs are useful for guiding decisions in chronic childhood asthma treatment.
    Journal of Asthma 10/2014; · 1.83 Impact Factor

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