December 9, 2009 — Inhaled corticosteroids (ICSs) may be superior to montelukast (MONT) in children and adolescents with asthma, according to the results of an extensive meta-analysis reported in the November 27 online issue of the Archives of Disease in Childhood.
"Asthma is one of the most common chronic diseases in children worldwide," write Jose A. Castro-Rodriguez, MD, PhD, from the School of Medicine, Pontificia Universidad Católica de Chile, and Gustavo J. Rodrigo, MD, from Hospital Central de las Fuerzas Armadas in Montevideo, Uruguay. "All current international guidelines recommend the use of low-dose (200-400 mcg of beclomethasone [BDP] or equivalent) [ICS] as the preferred controller therapy, with leukotriene receptor antagonist (LTRA) as an alternative, for the management of persistent asthma in children (5-11 years of age) and adolescents.... The objective of this systematic review is to compare the efficacy of ICS vs. [MONT] (the most common LTRA use in children worldwide) and vs. MONT add-on to ICS in schoolchildren and adolescents with persistent asthma."
A search of Medline, Embase, and Central databases identified randomized, prospective, controlled trials published from January 1996 to November 2009. Inclusion criteria were a minimum of 4 weeks of ICS vs MONT and of ICS vs MONT+ICS, with primary outcome of asthma exacerbations requiring systemic corticosteroids. Secondary outcomes were pulmonary function, study withdrawal or hospitalization because of asthma exacerbations requiring systemic corticosteroids, change in symptoms score, rescue-medication-free days, albuterol use, adverse effects, and adherence.
Inclusion criteria were met in 18 of 124 studies identified. Of these 18 studies, which enrolled a total of 3757 patients, 13 compared ICS vs MONT, 3 compared ICS vs MONT+ICS, and 2 compared ICS vs MONT vs ICS+MONT.
Compared with patients receiving MONT, those receiving an ICS had a significantly decreased risk for asthma exacerbations requiring systemic corticosteroids (relative risk [RR], .83; 95% confidence interval [CI], .72 - .96; P = .01). This finding appeared to be independent of study quality, sponsorship, and study duration, based on post hoc analysis. Children treated with an ICS also fared better than those treated with MONT in terms of pulmonary function (final forced expiratory volume in 1 second [FEV1] percentage predicted, change from baseline FEV1 percentage, final morning PEF) and clinical parameters (albuterol use, symptom score, rescue medication-free days, and study withdrawals resulting from asthma exacerbations requiring systemic corticosteroids).
In 2 studies comparing MONT as add-on therapy to ICS vs ICS alone, there was no significant difference in primary or secondary outcomes.
"Schoolchildren and adolescents with mild-persistent asthma treated with ICS had less ... [asthma exacerbations requiring systemic corticosteroids] and better lung function and asthma control than with MONT," the review authors write. "There is insufficient data to determine if the addition of MONT to ICS improves outcome."
Limitations of this review are that the analysis of the main outcome was based on only 7 studies (representing 65% of the total sample) and that stratification of studies based on different relevant factors was not always possible.
Arch Dis Child. Published online November 27, 2009.
According to the 2007 Guidelines for the Diagnosis and Management of Asthma from the National Heart, Lung, and Blood Institute, the preferred controller treatment for persistent asthma in children aged 5 to 11 years and adolescents is an ICS, whereas the alternative treatment is leukotriene receptor antagonist.
A meta-analysis by Ducharme and di Salvio, published online July 24, 2004, in the Cochrane Database of Systematic Reviews, found that an ICS vs leukotriene receptor antagonist was more effective in decreasing the number of asthma exacerbations requiring systemic corticosteroids. A meta-analysis by Ducharme, published online July 23, 2001, in the Cochrane Database of Systematic Reviews, noted that adding leukotriene receptor antagonist treatment to ICS treatment vs ICS treatment alone did not reduce the exacerbations requiring systemic corticosteroids.
This systematic review includes subsequent studies in children with mild to moderate persistent asthma to compare treatment with ICS vs leukotriene receptor antagonist (MONT) vs MONT added to ICSs for the prevention of severe asthma exacerbation requiring systemic corticosteroids, improvement in lung function, and improvement in asthma control.