Question

• In the pediatric population with intermittent and mild persistent asthma, do leukotriene receptor antagonists improve morbidity and quality of life? Are they safe?

Clinical Bottom Lines

1. Treatment with 5mg of montelukast (Singulair) resulted in statistically significant improvement in baseline FEV₁ in the treatment group (8.23%) at the end of the treatment period in comparison with the placebo group (3.58%). However, the absolute improvement was from FEV₁ of 1.85 to 2.01 vs. 1.85 to 1.93 for treatment and placebo respectively. Several other factors such as morning peak flows, quality of life ratings and blood eosinophilia likewise demonstrated a statistically significant difference.¹
2. Number needed to treat (NNT) to prevent a single asthma exacerbation was 9 over the 8-week course.
3. The drug showed rapid and sustained difference in the frequency of prn beta-agonist use.
4. The drug was safe with no statistical difference in adverse side effects between the two groups over the 8-week treatment period.

Summary of Key Evidence

1. 336 children, ages 6-14, with baseline FEV₁ of 50-85% of predicted and using beta-agonists on a regular basis were randomized to treatment (n=201) and placebo (n=135).
2. Primary end-points were change in baseline FEV₁, peak flow, frequency of prn beta-agonist use, quality of life ratings, days of school missed and numbers of asthma exacerbations.
3. Study was powered to detect a 7.1% change in baseline FEV₁ based on a sample size of 240.
4. Very low drop-out rate with n=189 (94%) of those treated and n=125 (92.6%) of those receiving placebo having completed the study.
5. There was a statistically significant improvement in the baseline FEV₁ of 8.23% in the active treatment group vs. 3.58% in the placebo group.
6. No statistical difference between groups in terms of incidence of adverse side effects.
7. There was a absolute risk reduction of 11% for having an asthma exacerbation over the 8 week course, resulting in a number needed to treat of 9.
8. Drug showed a rapid and sustained effect in lowering the use of prn beta-agonists over the entire 8-week course.

Additional Comments

• Although the study demonstrated an 8.53% improvement in baseline FEV1, the absolute change was 1.85 to 2.01 vs. 1.85 to 1.93 which is of unclear clinical significance.
• While the study demonstrated an 11% absolute risk reduction for asthma exacerbations, it is important to note that an "exacerbation" was defined as anything from >70% increased use of MDI's to unexpected need for hospitalization. While it is clear that the costs of treating 9 people for 8 weeks clearly outweigh the costs associated with a hospital admission (particularly if it includes a stay in the intensive care unit), it is not as clear whether there is a cost benefit for averting increased use of MDI's or of nocturnal awakenings. Thus, it is not possible to comment on the cost effectiveness of this particular treatment given the limited data in reported in the study.
• While the immediate safety profile appears promising, long-term effects of chronic use are unclear. Thus, it is difficult to completely endorse this treatment from a side effect point of view.

Citation

1. Knorr B, Matz J, et al. Montelukast for chronic asthma in 6- to 14-year-old children. A randomized, double-blind trial. JAMA. 279(15):1181-1187, 1998.

CAT Author: Michael Gill, MD, PhD

CAT Appraisers: John G. Frohna, MD

Date appraised: August 5, 1998