Table 1.
Systematic reviews and reviews of effectiveness and clinical efficacy of montelukast, with references listed in chronological order according to the year of publication
| Population | Design | Efficacy and adverse effects | Remarks | References |
|---|---|---|---|---|
| Infants <24 months | Systematic review of RCTs and quasi-RCTs. 1,430 infants | Montelukast may reduce the frequency of postbronchiolitic wheezing without causing significant side effects, but that it has no effects on decreasing incidences of recurrent wheezing, symptom-free days, or the associated usage of corticosteroid in postbronchiolitis patients. Side effects of rash, vomiting, and insomnia caused by montelukast occurred in 1.5% of patients analyzed. | Small number of enrolled participants and inability to pool all clinical outcomes. | 67* |
| Children and adults | Systematic review of RCTs | Improvements in symptoms and small-airways function after treatment with montelukast, whereas no relation existed with FEV1 improvement. Adverse effects not mentioned. | Improvements in clinical and laboratory parameters demonstrated. | 54 |
| 1–18 years | RCTs: addition of antileukotriene (montelukast) to ICSs in mild to moderate asthma | No evidence to support efficacy and safety of LTRAs as add-on therapy to low-dose ICS for children with uncontrolled asthma symptoms. | Low risk of bias, 5 trials of 559 children, conclusions valid. | 83 |
| Children and adults | 17 RCTs | In adults with asthma that is inadequately controlled on low doses of ICSs and showing significant reversibility with beta 2-agonists, LABA is superior to LTRA in reducing oral steroid treated exacerbations. Differences favoring LABA in lung function, functional status, and quality of life scores are generally modest. There is some evidence of increased risk of severe adverse effects with LABA. The findings support the use of a single inhaler for the delivery of LABA and ICSs. Unable to draw conclusions about which treatment is better as add-on therapy for children. | LTRA has no significant efficacy or adverse effects | 62* |
| Children | Review article | ICSs are the treatment of first choice for the maintenance therapy of childhood asthma, irrespective of age or clinical phenotype, and the risk of asthma exacerbations and hospitalizations is seven times higher in children on montelukast treatment than in those receiving ICSs. | Good quality convincing trials are cited to support the conclusions. | 63 |
| Children | PubMed + Medline (1966–2006) search: double-blind randomized, placebo-controlled parallel-group study | Usefulness of primary care initiated or parent-led short courses of oral montelukast as adjunctive therapy for mild asthma exacerbations in children older than 2 years. No adverse effects. | Five RCTs included. Level of evidence generally 1B. | 84 |
| Children and adults | Retrospective analysis of four previously reported clinical trials | Inhaled fluticasone propionate/salmeterol were consistently greater compared to montelukast. No adverse effects. | Not a clinical trial in itself. | 85 |
| Children | Systematic review with meta-analysis of 18 relevant studies. Some already mentioned in this table | Schoolchildren and adolescents with mild to moderate persistent asthma. ICS had less asthma exacerbations, better lung function and asthma control than with montelukast. Insufficient data to determine whether the addition of montelukast to ICS improves outcome. No adverse effects. | Well-performed meta-analysis to demonstrate ICS superior to montelukast. | 86 |
| 15–45 years of age | Three randomized, double-blind, crossover trials evaluating single-dose montelukast 10 mg or placebo in patients (n=160) with EIB | Pooled regression analysis. No relevant clinical or adverse effects | Not a direct evaluation of effectiveness. | 87* |
| Children | Comparative systematic review RCTs | Compared with long-acting beta adrenoceptor agonists, LTRAs produce persistent attenuation of EIB and possess an additional effect with rescue short acting adrenoceptor agonists therapy in asthmatic patients with persistent EIB. A disadvantage of montelukasts is a nonresponse phenomenon. | Sign criteria (evidence level and grades of recommendation) employed. No additional statistical analyses. | 65 |
| Children | Review of eight studies | ICSs are the first choice in pediatric persistent asthma. Montelukast monotherapy as an alternative treatment for the prevention of mild persistent pediatric asthma. | Only few studies included. | 88 |
| Mean (SD) age 9.6 (2.1) years | Multivariate analysis | Long-term outcomes with ICS therapy better compared with treatment with leukotriene receptor antagonists. No adverse effects. | ICS is better, but montelukast still useful. | 60 |
| Adolescents and adults | Systematic review of 13 studies | Montelukast as add-on therapy to ICSs in the treatment of mild to moderate asthma improves control of asthma compared with ICS monotherapy. No significant adverse effects. |
Montelukast is useful as add-on therapy. | 89 |
| School-age children | Meta-analyses of five randomized double-blind efficacy studies | ICS is the preferred first-line controller therapy for mild to moderate persistent childhood asthma to montelukast. | Montelukast not as first-line controller. | 90 |
| Children and adults | Review | Leukotriene receptor antagonists (montelukast and zafirlukast) are beneficial across a range of asthma severities and may have a particular role in exercise-induced asthma, aspirin-sensitive asthma, and individuals with concomitant allergic rhinitis. Hypersensitivity reactions, arthralgia, pulmonary eosinophilia, gastrointestinal disturbances, sleep disorders, respiratory infections, hallucinations, seizures, and raised liver enzyme levels are adverse effects. | Unrestricted educational grant from AstraZeneca LP. Two LTRAs. Side effects listed. | 68 |
| Adults | Meta-analysis: eleven trials including 6,030 participants | In asthmatic adults inadequately controlled on low doses of ICSs, the addition of LABA is superior to LTRA (montelukast or zafirlukast) for preventing exacerbations requiring systemic steroids, and for improving lung function, symptoms, and the use of rescue beta 2-agonists. No adverse effects. | Montelukasts are inferior to LABA. | 91 |
| Children and adults | Systematic literature review of 11 clinical studies | Combination therapy with ICS and LABA was found to be more efficacious and cost effective compared with ICS alone or alternative combinations of controller medications. Montelukast is inferior. No adverse effects on montelukast. | Evaluates combination therapy with ICS plus LABA than montelukast. | 92 |
| Children and adults | Retrospective analysis of matched cohort of 1,216 patients | Use of ICS/montelukast compared with ICS/salbutamol resulted in similar odds of oral corticosteroid fills, decreased odds of emergency department visits and asthma related hospitalizations but higher utilization of short acting beta agonist. No adverse effects. |
Large retrospective cohort. Some efficacy demonstrated. | 93 |
| Adults | Literature search on asthma controller therapy during pregnancy | Human pregnancy data for leukotriene modifiers (montelukast, zafirlukast, and zileuton) are limited to their reported use by nine pregnant women. No increased risk of preterm delivery caused by leukotriene modifiers was reported in these women.93 Animal studies show no teratogenicity with montelukast or zafirlukast at doses much higher than the maximum recommended human daily doses. In contrast, zileuton has demonstrated adverse effects in fetal rats and a 2.5% incidence of cleft palate in rabbits at a dose equal to the maximum recommended human daily dose on a milligram per meters squared basis. The leukotriene modifiers (zafirlukast and montelukast) are rated pregnancy category B, based on safety in animal reproduction studies. Zileuton carries a pregnancy category C rating that is based on demonstrated risk in animal studies. | Only nine pregnant women; no adverse effects on perinatal outcome. | 95 |
| Children and adults | 12 RCTs | In asthmatic adults inadequately controlled on low doses of ICSs, the addition of LABA is superior to LTRA for preventing exacerbations requiring systemic steroids and for improving lung function, symptoms, and use of rescue beta 2-agonists. | LTRA is inferior to LABA as add-on therapy. | 96 |
| Children and adults | Literature review | LTRAs (montelukast, zafirlukast, and zileuton) may be used in patients with mild persistent asthma as well as in combination with other asthma medications at all levels of disease severity for long-term maintenance of asthma control. | A review, not a study. | 64 |
| Children and adults | Review of controlled clinical studies in English | Leukotrienes should be considered as a therapeutic option or as additive therapy in patients with mild to severe asthma. No adverse effects. | A review. | 97 |
| Primarily pregnant women | Review of controlled clinical studies in English | Safety issues: both zafirlukast and montelukast carry pregnancy category B classification whereas zileuton carries pregnancy category C classification. The most common adverse effects observed in clinical trials were headache, pharyngitis, abdominal pain, dyspepsia, and cough. |
Review. Provides some data on pregnancy adverse effects. | 69 |
| Adults | Retrospective cohort analysis of a primary care database in the UK (n=94) | Patients using chronic montelukast therapy experienced a statistically significant (P<0.05) reduction in the use of short-acting beta agonists and antibiotics, suggesting improvement in asthma control. Chronic use of montelukast therapy is associated with a reduction of concomitant drug therapy costs. | Mainly cost analysis study. | 98 |
| Children and adults | MEDLINE search (up to May 1999) on relevant English language publications | Montelukast is indicated for the prophylaxis of chronic asthma in adults and children (≥6 years). It may be considered as first-line therapy in patients with mild persistent asthma or for additional control in patients who are still symptomatic while receiving treatment with ICSs. It may also be used for additional control in aspirin-sensitive asthmatic patients. Consideration may be given for using montelukast to allow tapering of the dose of ICSs. Chronic treatment with montelukast can provide additional control of symptoms during exercise, but inhaled beta 2-agonists remain first-line therapy for prophylaxis and treatment. | Many newer studies not included. | 66 |
Note:
*
Additional references identified.
Abbreviations: EIB, exercise-induced bronchoconstriction; FEV1, forced expiratory volume in 1 second; ICS, inhaled corticosteroid; LABA, long-acting beta 2-agonist; LTRA, leukotriene receptor antagonist; RCT, randomized controlled trial; SD, standard deviation.