Current issues of ACP Journal Club are published in Annals of Internal Medicine


Montelukast moderately decreased asthma symptoms in children with persistent asthma


ACP J Club. 2002 May-Jun;136:102. doi:10.7326/ACPJC-2002-136-3-102

Related Content in the Archives
• Correction: Montelukast moderately decreased asthma symptoms in children with persistent asthma

Source Citation

Knorr B, Franchi LM, Bisgaard H, et al. Montelukast, a leukotriene receptor antagonist, for the treatment of persistent asthma in children aged 2 to 5 years. Pediatrics. 2001 Sep;108:e48. [PubMed ID: 11533366] (All 2002 articles were reviewed for relevancy, and abstracts were last revised in 2008.)



In children with persistent asthma, is montelukast a well-tolerated and effective therapeutic option?


Randomized {allocation concealed*}†, blinded (patients, clinicians, and {data collectors}†),* placebo-controlled trial with 12-week follow-up.


93 centers in Africa, Australia, Europe, North America, and South America.


689 children who were 2 to 5 years of age (mean age 4 y, 59% boys, 56% white), had ≥ 3 episodes of asthma symptoms in the previous year, had a total asthma symptom score ≥ 1 (of 24) for ≥ 8 days during the 2-week placebo baseline period, and used β-agonists for ≥ 8 days during the placebo baseline period. Exclusion criteria included asthma intubation and emergency department treatment or hospitalization for asthma within 1 month before the study. Follow-up ranged from 98% to 100% for safety and from 81% to 96% for other outcomes.


Patients were allocated to montelukast, 4-mg chewable tablet (n = 461), or to placebo tablet (n = 228). Tablets were given once daily at bedtime for 12 weeks.

Main outcome measures

Safety, asthma symptoms, and days with β-agonist use and without asthma.

Main results

Analysis was by intention to treat for {safety}† and effectiveness end points. The montelukast and placebo groups did not differ for frequency of overall adverse effects or individual adverse effects except for asthma, which occurred more frequently in the placebo group (30% vs 38%, difference 8.0%, 95% CI 0.18 to 16). The groups did not differ for discontinuation of treatment because of adverse effects (3.5% vs 3.1% {P > 0.999}‡). Groups did not differ for ≥ 1 laboratory adverse effect (3.6% vs 5.4%, {P = 0.31}‡). Montelukast decreased asthma symptom scores (Table) and days with β-agonist use (49% vs 55%, P = 0.001) and increased days without asthma (34% vs 28%, P = 0.002) more than did placebo.


In children with persistent asthma, montelukast was well tolerated, decreased asthma symptom scores and β-agonist use, and increased days without asthma.

*See Glossary.

†Information provided by author.

P values provided by author.

Source of funding: Merck Research Laboratories.

For correspondence: Dr. B. Knorr, Respiratory & Allergy, Merck Research Laboratories, Rahway, NJ, USA.

Table. Montelukast vs placebo at 12 wk in children with persistent asthma

Outcomes§ Mean decrease in score from baseline Least-square mean difference (CI)
Montelukast Placebo
Overall daytime asthma symptom score|| 0.37 0.26 0.12 (0.04 to 0.20)
Overnight asthma symptom score|| 0.46 0.37 0.11 (0.01 to 0.21)

§No symptoms = 0; severe symptoms = 4 or 5.
||A correction was made at this point in the table. See Notices and Corrections for details.


The well-done, multicenter study by Knorr and colleagues showed that montelukast led to greater improvement in asthma symptoms and control than did placebo. These findings have been supported by a subsequent study showing that montelukast also reduces asthma exacerbations (1). However, in these trials, montelukast was compared with placebo. In contrast, montelukast is less effective than inhaled steroids (2) and adding montelukast to inhaled steroids is inferior to increasing the inhaled steroid doses (3).

For safety, caution is always needed when using tablets in young children. The American Academy of Pediatrics notes that safe swallowing can be difficult for young children for reasons of anatomy, experience, and judgment (4). However, many chewable tablets are approved for use in children ≥ 2 years of age (5). The study by Knorr and colleagues had a 90% probability of detecting an adverse drug reaction (ADR) of 7.8% in the montelukast group and 1% in the placebo group. However, the likelihood of detecting a less common ADR would be about 5% for an event occurring in 1 in 10000 patients (6). Thus, rare ADRs can only be determined by post-marketing surveillance.

What are the clinical implications? The National Asthma Education and Prevention program expert panel has recommended leukotriene modifiers as an alternative therapy for persistent asthma, although inhaled steroids are recommended as preferred therapy in children of all ages (7). The study by Knorr and colleagues has provided much of the basis for this recommendation for children under years of age 5.

Lynnette J. Mazur, MD, MPH
University of Texas–Houston Health Science Center
Houston, Texas, USA


1. Bisgaard H, Zielen S, Garcia-Garcia ML, et al. Montelukast reduces asthma exacerbations in 2- to 5-year-old children with intermittent asthma. Am J Respir Crit Care Med. 2005;171:315-22. [PubMed ID: 15542792]

2. Vidal C, Fernandez-Ovide E, Pineiro J, Nunez R, Gonzalez-Quintela A. Comparison of montelukast versus budesonide in the treatment of exercise-induced bronchoconstriction. Ann Allergy Asthma Immunol. 2001;86:655-8. [PubMed ID: 11428738]

3. Jat GC, Mathew JL, Singh M. Treatment with 400 microg of inhaled budesonide vs 200 microg of inhaled budesonide and oral montelukast in children with moderate persistent asthma: randomized controlled trial. Ann Allergy Asthma Immunoll 2006;97:397-401. [PubMed ID: 17042148]

4. Widome MD, ed. Injury Prevention and Control for Children and Youth. 3d ed. Elk Grove Village, IL: The Academy; 1997.

5. Michele TM, Knorr B, Vadas EB, Reiss TF. Safety of chewable tablets for children. J Asthma. 2002;39:391-403. [PubMed ID: 12214893]

6. Hanley JA, Lippman-Hand A. If nothing goes wrong, is everything all right? Interpreting zero numerators. JAMA. 1983;249:1743-5. [PubMed ID: 6827763]

7. Expert panel report 3: guidelines for the diagnosis and management of asthma. National Heart, Lung, and Blood Institute. 2007.