Appendices

Randomised placebo-controlled trials

Knorr et al., 2001⁸

Montelukast 4 mg once daily at bedtime for 12 weeks in pre-school children with mild-to-moderate persistent asthma (n=689)

Montelukast superior to placebo on: percentage asthma-free days, daytime asthma symptoms, night-time asthma symptoms, days with asthma symptoms, need for SABA or oral corticosteroids, physician's global evaluation

No significant difference vs placebo in exacerbations rate, caregiver's global evaluation, quality of life

Benefits observed from first day

No difference vs placebo in adverse event rate

Knorr et al., 1998⁹

 Becker et al., 2004²²

Montelukast 5 mg once daily at bedtime for 8 weeks in school children with persistent asthma (n=336)

Included children with moderately severe (FEV150-85% predicted) asthma

One-third taking ICS

Montelukast superior to placebo on: FEV1improvement, SABA use, days with asthma exacerbations (21% vs 26%), quality of life

No significant difference vs placebo on: absenteeism from school, nocturnal awakening, daytime asthma symptom score.

Onset of action rapid and sustained

No difference vs placebo in adverse event rate

In subgroup with milder asthma (FEV1> 75% predicted), montelukast superior to placebo on: FEV1improvement, PEF, night-time wakening, quality of life

Phipatanakul et al., 2002⁴²

School children with asthma triggered by exposure to cat allergens (n=18)

Montelukast superior on: FEV1response to allergen exposure, duration of challenge tolerated

No significant difference vs placebo for upper respiratory

response

Johnston et al., 2007³¹

6-week trial of montelukast during predictable annual epidemic of asthma exacerbations in children taking usual treatment (n=194)>

Montelukast superior to placebo on following outcome measures: reduction in days with worse asthma symptoms and reduction in unscheduled physician visits for asthma Benefit seen in both ICS and non-ICS subgroups

Randomised comparative trials

Garcia Garcia et al., 2005¹¹

Montelukast 5 mg once daily vs fluticasone 100 mcg twice daily in school children with mild persistent asthma for 12 months (n=994)

Designed to demonstrate non-inferiority for primary outcome: change

from baseline in % days free of rescue

medications (e.g. SABA, systemic

corticosteroids)

Montelukast not inferior to ICS on primary outcome

Fluticasone superior on: FEV1, days without SABA, quality of life, systemic corticosteroid requirement, acute asthma episodes

Both montelukast and fluticasone well tolerated

Luskin et al., 2003²⁵

Montelukast vs fluticasone in school children with mild persistent asthma (n=104)

12-month prospective open-label observational study

Montelukast and fluticasone equally effective on: emergency visits, hospitalisation, symptoms at study completion, SABA use, oral prednisolone use.

Montelukast superior on adherence  

Sorkness et al., 2007²⁶

Montelukast once daily vs fluticasone 100 mcg twice daily for 48 weeks in school children with mild-to-moderate persistent asthma  

Fluticasone superior on: symptom-free days, SABA use, improvement in number of asthma control days, improvement in episode-free days, FEV1, morning and evening PEF

No difference for growth over 48 weeks

Zeiger et al., 2006²⁷

Montelukast vs fluticasone for 16 weeks in school children with mild-to-

moderate persistent asthma

Fluticasone superior to montelukast on: number of asthma control days, Asthma Control Questionnaire,

SABA use, FEV₁, peak expiratory flow

Ostrom et al., 2005²⁸

Montelukast 5 mg once daily vs fluticasone 50 mcg twice daily for 12 weeks in school children (n=342) with moderate-to-severe persistent asthma (baseline FEV160-85% predicted)

Fluticasone superior to montelukast on: FEV1, morning and evening PEF, percentage rescue-free days, night-time symptom score, mean total symptom score, SABA use

Jat et al., 2006²⁹

Combination montelukast 5 mg once + budesonide 200 mcg daily vs budesonide 400 mcg/day alone in children with moderate persistent asthma

Similar efficacy on: FEV1, asthma symptom scores Budesonide 400 mcg/day markedly superior to montelukast plus low-dose budesonide on exacerbation rate (33.3% vs 9.1%; P < 0.01)

Lemanske et al., 2005²⁴

Comparison of three step-up therapies in random order in children (6–17 years) with uncontrolled asthma despite 200 mcg fluticasone daily (n=182): 500 mcg fluticasone daily vs 200 mcg fluticasone + 100 mcg salmeterol daily vs 100 mcg fluticasone + montelukast  

Response to step-up treatments was highly variable.
 
Probability of ‘best response’ greatest with salmeterol (45%), and approximately equal for montelukast (28%) and increased dose of ICS (27%). However, FEV1 included in the outcome measure, thus favouring the salmeterol arm.

Randomised placebo-controlled trials

Bisgaard et al., 2003³⁰

Long-term (12 months) montelukast in pre-school children with intermittent asthma and a history of recurrent viral-induced exacerbations taking ICS (n=549)

Montelukast superior to placebo on: exacerbation rate, ICS requirement
Number of positive viral tests too low to permit correlation of reduction exacerbations with prevention of viral-induced episodes

Robertson et al., 2007³

12-month study of parent-initiated montelukast course commenced at onset of viral infection or asthma symptoms in school children with intermittent asthma

Montelukast superior to placebo on: reduction in symptoms, days off school, need for doctor visits Non-significant trend favouring montelukast for: specialist attendances and hospitalisations, duration of episode, SABA use, prednisolone use

Randomised comparative trials 

Bacharier et al., 2008³²

12-month study of comparing 7-day course of budesonide via nebuliser vs montelukast vs placebo (in addition to SABA) at onset of respiratory infections in preschool children (12–59 months) with moderate-to-severe intermittent wheezing (n=238) 

No difference between treatment groups on following outcome measures: proportion of episode-free days, oral corticosteroid use, health care use, quality of life, linear growth

Both budesonide and montelukast reduced symptoms and interference with activity, compared with placebo 

Randomised placebo- controlled trials

Kim et al., 2005³⁵

Montelukast taken for 8 weeks in children with exercise-induced asthma (n=64)

Montelukast + ICS and montelukast monotherapy superior to other treatments on FEV1 reduction after exercise challenge

Randomised comparative trials 

Stelmach et al., 2008³⁷

A 4-week comparison of four treatments: eformoterol + ICS vs montelukast + ICS vs ICS vs montelukast vs placebo in school-aged children with atopic asthma (n=100) 

No difference between treatment groups on following outcome measures: proportion of episode-free days, oral corticosteroid use, health care use, quality of life, linear growth

Both budesonide and montelukast reduced symptoms and interference with activity, compared with placebo 

Fogel et al., 2010³⁸

4-week comparison of montelukast vs salmeterol in addition to ICS in school-aged children with persistent asthma and exercise-induced asthma (n=154) 

Montelukast superior to salmeterol on following outcome measures: FEV1 reduction, use of SABA after exercise challenge 

FEV₁, Forced expiratory volume in 1 second; ICS, inhaled corticosteroids; PEF, peak expiratory flow; SABA, short-acting beta2 agonist.