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10 September 2010
A meta-analysis has found that inhaled corticosteroids are significantly more effective than montelukast for preventing severe asthma exacerbations requiring systemic corticosteroids in schoolchildren and adolescents with mild-moderate asthma.
Level of evidence:
Level 1 (good quality patient-oriented evidence) according to the SORT criteria.
Action
Health professionals should follow the BTS/SIGN guideline on the management of asthma. For patients not adequately controlled on a short-acting beta2-agonist when required (step 1), inhaled corticosteroids (ICSs) are the first choice regular preventer therapy (step 2). A leukotriene receptor antagonist (LTRA e.g. montelukast) may be considered in children under five years if an ICS cannot be used.
A proportion of patients with asthma may not be adequately controlled on an ICS alone at step 2. For adults and children aged 5 to 12 years, the addition of a long-acting beta2-agonist (LABA e.g. salmeterol or formoterol) to an ICS should be considered next (step 3). For children under five years, the first choice add-on therapy to an ICS is a LTRA. However, before adding or changing treatment, practitioners should check concordance with existing therapy, check the patient’s inhaler technique and eliminate trigger factors.
What is the background to this?
This systematic review and meta-analysis of RCTs compared the efficacy of ICSs versus montelukast alone and added to an ICS in schoolchildren and adolescents with mild-moderate persistent asthma.
What does this study claim?
The study found that schoolchildren and adolescents taking ICSs (200–400 micrograms per day of beclometasone diproprionate or equivalent[BDP]) had fewer asthma exacerbations requiring systemic corticosteroids compared with those taking montelukast (5–10mg per day) (21.3% vs. 25.6% respectively; NNT 24, 95%CI 13 to 110; RR 0.83, 95%CI 0.72 to 0.96, P=0.01). Twenty four children would need to be treated with an ICS instead of montelukast to prevent one additional asthma exacerbation requiring systemic corticosteroids over 8 to 56 weeks. Children taking ICSs also had better lung function and asthma control than children taking montelukast.
There was no significant difference in the number of patients experiencing exacerbations requiring systemic corticosteroids between ICS and montelukast plus ICS (RR 0.53, 95%CI 0.10 to 2.74, P=0.45). However, this result was based on only two studies, which had evidence of statistical heterogeneity.
So what?
This meta-analysis supports the BTS/SIGN asthma guideline for the management of asthma. ICSs are the first choice regular preventer therapy for adults and children for achieving overall treatment goals. They should be considered for patients with any of the following asthma-related features:
- one or more exacerbations of asthma requiring oral corticosteroids in the last two years
- using inhaled beta2-agonists three times a week or more
- symptomatic three times a week or more
- waking at least one night a week.
A proportion of patients with asthma may not be adequately controlled on an ICS alone at step 2. For adults and children aged 5 to 12 years, the addition of a LABA (salmeterol or formoterol) to an ICS should be considered (step 3). LABAs should be prescribed in line with MHRA advice, only in conjunction with regular ICSs, and stopped if there is no response. If asthma control is still inadequate despite trial of a LABA, and the dose of ICS has been increased up to 400 micrograms per day BDP, a trial of a LTRA or theophylline SR may be considered. For children under five years, a LTRA (e.g. montelukast) is the first choice add-on therapy to an ICS. There is little evidence to support treatment options in this age group.
Design: Meta-analysis of 18 RCTs including 3,757 children and adolescents.
Patients: Children aged less than 18 years with a clinical diagnosis of asthma for at least six months before study entry.
Intervention and comparison: Participants had been treated for at least four weeks with ICS (budesonide, beclometasone, fluticasone or triamcinolone) compared with montelukast or montelukast plus ICS. The dose of ICS was maintained throughout the intervention period.
Outcomes: The primary outcome was asthma exacerbations defined as worsening symptoms that required systemic corticosteroid use. Secondary outcomes were lung function, withdrawal/hospitalisation due to asthma exacerbations requiring systemic corticosteroids, change in symptoms score, rescue-medication-free days, salbutamol use, adverse effects and adherence.
Results: One study included patients aged 2 to 8 years. The remainder included children aged 5 to 18 years. The mean age was 9.7 years (63% male) and the average baseline FEV1 was 81% of predicted normal values. Thirteen studies compared ICS vs. montelukast; three studies compared ICS vs. montelukast plus ICS; two studies compared ICS vs. montelukast vs. ICS plus montelukast. Six trials were longer than 24 weeks and eight were of high methodological quality.
Patients receiving ICS (200–400 micrograms per day of beclometasone diproprionate or equivalent) showed a significantly lower risk for asthma exacerbations defined as worsening symptoms that required systemic corticosteroid use than those with montelukast (5–10mg per day) (7 RCTs, n=2,429; 21.3% vs. 25.6% respectively; RR 0.83, 95%CI 0.72 to 0.96, P=0.01). Children treated with ICS had a significantly better function (final FEV1% predicted, change from baseline FEV1%, final morning peak expiratory flow) and better clinical parameters (salbutamol use, symptom score, rescue medication-free days, all cause withdrawals) versus montelukast.
No significant difference in primary (RR 0.53, 95%CI 0.10 to 2.74, P=0.45) or secondary outcomes was found when montelukast was added on to ICS versus ICS alone. However, these analyses were based on only two studies (n=610).
Sponsorship: The authors have received sponsorship from various pharmaceutical companies involved in the manufacture of asthma medication. However, no sponsorship from institutions or the pharmaceutical industry was provided to conduct this study.
More information can be found on the asthma section of NPC.
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