Intermittent or daily montelukast versus placebo for episodic asthma in children.

BACKGROUND: No standard, optimal treatment exists for severe intermittent (ie, episodic) asthma in children. However, evidence suggests that both daily and episode-driven montelukast are effective for this phenotype. OBJECTIVE: To assess the regimen-related efficacy of montelukast in treating pediatric episodic asthma. METHODS: A multicenter, randomized, double-blind, double-dummy, parallel-group, 52-week study was performed in children 6 months to 5 years of age comparing placebo with two regimens of montelukast 4 mg: (1) daily; or (2) episode-driven for 12 days beginning with signs/symptoms consistent with imminent cold or breathing problem. The main outcome measure was the number of asthma episodes (symptoms requiring treatment) culminating in an asthma attack (symptoms requiring physician visit, emergency room visit, corticosteroids, or hospitalization). RESULTS: Five hundred eighty-nine patients were randomized to daily montelukast, 591 to intermittent montelukast, and 591 to placebo. Compared with placebo, no significant difference was seen between daily montelukast (P = .510) or intermittent montelukast (P = .884) in the number of asthma episodes culminating in an asthma attack over 1 year. Daily montelukast reduced symptoms over the 12-day treatment period of asthma episodes compared with placebo (P = .045). Beta-agonist use was reduced with both daily (P = .048) and intermittent montelukast (P = .028) compared with placebo. However, because of prespecified rules for multiplicity adjustments (requiring a positive primary endpoint), statistical significance for secondary endpoints cannot be concluded. All treatments were well tolerated. CONCLUSIONS: Montelukast did not reduce the number of asthma episodes culminating in an asthma attack over 1 year in children 6 months to 5 years of age, although numerical improvements occurred in some endpoints.

Safety and tolerability of montelukast in placebo-controlled pediatric studies and their open-label extensions.

BACKGROUND: Montelukast is a potent leukotriene-receptor antagonist administered once daily that provides clinical benefit in the treatment of asthma and allergic rhinitis in children and adults. Because of its wide use as a pediatric controller, there is a need for a further review of the safety and tolerability of montelukast in children. OBJECTIVE: To summarize safety and tolerability data for montelukast from previously reported as well as from unpublished placebo-controlled, double-blind, pediatric studies and their active-controlled open-label extension/extended studies. METHODS: These studies evaluated 2,751 pediatric patients 6 months to 14 years of age with persistent asthma, intermittent asthma associated with upper respiratory infection, or allergic rhinitis. These patients were enrolled in seven randomized, placebo-controlled, double-blind registration and post-registration studies and three active-controlled open-label extension/extended studies conducted by Merck Research Laboratories between 1995 and 2004. RESULTS: Montelukast was well tolerated in all studies. Clinical and laboratory adverse experiences for patients treated with montelukast were generally mild and transient. The most frequent clinical adverse events for all treatments (placebo, montelukast, active control/usual care) in virtually all studies were upper respiratory infection, worsening asthma, pharyngitis, and fever. CONCLUSION: The clinical and laboratory safety profile for montelukast was similar to that observed for placebo or active control/usual care therapies. The safety profile of montelukast did not change with long-term use.