Clinical evidence for montelukast use in children

Persistent asthma

Intermittent asthma

Exercise-induced asthma

Evidence for the efficacy of montelukast in children with each clinical pattern of asthma is summarised in Appendix 1.

Persistent asthma

Large placebo-controlled trials of montelukast once daily in preschoolers and in school-aged children with persistent asthma have demonstrated efficacy on clinical outcomes including increase in proportion of asthma-free days, reduction in daytime and night-time asthma symptoms, and reduction in requirement for SABA and oral corticosteroids.^13,14 In children old enough to perform spirometry reliably, placebo-controlled trials have also demonstrated efficacy on lung function variables.¹⁴ The onset of action of montelukast is rapid and sustained, with benefits observed within the first day of treatment.¹³

The greatest benefits have been observed in children with relatively mild asthma.¹⁷

Studies in children with moderately severe persistent asthma have consistently reported less benefit. In placebo-controlled studies that included children with moderately severe asthma, montelukast did not reduce exacerbation rates or improve parent-reported measures in pre-schoolers¹³ or reduce night-time wakening due to asthma, symptoms scores or school absences in school-aged children.¹⁴ Based on data from placebo-controlled trials, it has not been possible to define clinical indicators that predict which children will benefit most from montelukast therapy.¹⁸ In children with mild persistent asthma, montelukast may be an alternative to low-dose ICS for improving clinically relevant measures of asthma control such as SABA requirement,¹⁶ emergency care visits and hospitalisation rates.¹⁹ However, ICS are more effective than montelukast on a range of outcome measures including lung function measures.¹⁶

In comparative studies that included children with moderate persistent asthma, ICS were superior to montelukast on clinical, lung function and quality-of-life outcome measures.^20–23

Although the clinical characteristics of children with mild-to-moderate persistent asthma who will benefit most from montelukast therapy are not yet well defined, there is some evidence that lung function response to montelukast, but not ICS, is predicted by younger age and shorter asthma duration. Children are more likely to respond to an ICS than to montelukast if they have stronger inflammatory markers, worse lung function and more symptoms.^{21, 24}

 

Children with mild persistent asthma should receive regular preventive therapy with LTRAs, cromones or low-dose ICS.1 Regular treatment with an ICS is recommended in children with moderate-to-severe persistent asthma.1

Intermittent asthma

Continuous montelukast once daily may reduce exacerbation rates and ICS requirement in pre-school children with intermittent asthma who have a history of recurrent exacerbations associated with respiratory infections.²⁵

Recent data also suggest that a short course of montelukast, introduced at the first signs of an asthma episode or upper respiratory tract infection, can achieve a small reduction in symptoms, school absence and medical consultations in preschool and school-aged children with intermittent asthma.³ However, no comparative studies have directly compared the effects of LTRAs commenced at the onset of exacerbations with short courses of high-dose ICS.

 

Children with infrequent intermittent asthma require treatment only during episodes. Acute asthma episodes should be managed with SABAs and oral corticosteroids. A short course of montelukast, introduced at the first signs of an asthma episode or upper respiratory tract infection, may reduce symptoms. Children with frequent intermittent asthma may benefit from regular preventive therapy with LTRAs, cromones or low-dose ICS. It is common for preventive treatment to be required only during the winter months.1

Exercise-induced asthma

Exercise-induced symptoms are commonly reported in children with asthma, but are not always due to asthma. The pathophysiology of exercise-induced bronchoconstriction involves the release of inflammatory mediators including cysteinyl leukotrienes in response to airway dehydration during exercise.²⁶ In adults, montelukast taken before exercise has been shown to cause a signifi cant reduction in the concentration of leukotriene in sputum.²⁷ Treatment with LTRAs lessens, but does not completely prevent, the post-exercise fall in FEV1 that is characteristic of exercise-induced asthma. Like cromones, they enable a more rapid recovery in lung function.²⁸

LTRAs can be effective as a single dose, but time to onset of therapeutic effect is variable and a loading dose may be required.²⁸ Protection against exercise-induced bronchoconstriction has been observed within 2 hours of taking montelukast.²⁹

Evidence from placebo-controlled trials in children with exercise-induced bronchoconstriction demonstrates that montelukast significantly reduces the fall in lung function in response to exercise challenge.^30–32 Protection is seen within 2 days (two doses) of commencing treatment.³¹

 

Montelukast is an alternative to SABA for exercise-induced asthma prophylaxis. Very frequent use of SABA taken before exercise (e.g. every day) should be avoided due to potential tolerance.33 Single-dose montelukast can be effective (e.g. taken the night before or at least 2 hours before exercise).29 In children taking regular montelukast as preventer, breakthrough exercise-induced asthma will typically resolve rapidly with no additional medication. If symptoms persist, SABA is rapidly effective.

 

Key findings from clinical trials* Persistent asthma There is substantial evidence that montelukast is an effective preventer therapy, compared with placebo, in children with persistent asthma. Montelukast may be an effective alternative to low-dose ICS or cromones in children with mild persistent asthma. There is less evidence to support the use of LTRAs in moderate-to-severe persistent asthma. Intermittent asthma Long-term montelukast treatment may protect against asthma exacerbations associated with respiratory infections. Short courses of montelukast, introduced at the first signs of an asthma episode or upper respiratory tract infection, can achieve a small reduction in symptoms and school absence. Exercise-induced asthma Montelukast protects against bronchoconstriction and fall in lung function in response to exercise challenge in children with exercise-induced bronchoconstriction. *This information based on clinical literature published up to February 2007 (search strategy described in Appendix 2)