Montelukast, a Leukotriene Receptor Antagonist, for the Treatment of Persistent Asthma in Children Aged 2 to 5 Years

Abstract

ABSTRACT. Background. The greatest prevalence of asthma is in preschool children; however, the clinical utility of asthma therapy for this age group is limited by a narrow therapeutic index, long-term tolerability, and frequency and/or difficulty of administration. Inhaled corticosteroids and inhaled cromolyn are the most commonly prescribed controller therapies for young children with persistent asthma, although very young patients may have difficulty using inhalers, and dose delivery can be variable. Moreover, reduced compliance with inhaled therapy relative to orally administered therapy has been reported. One potential advantage of montelukast is the ease of administering a once-daily chewable tablet; additionally, no tachyphylaxis or change in the safety profile has been evidenced after up to 140 and 80 weeks of montelukast therapy in adults and pediatric patients aged 6 to 14 years, respectively.To our knowledge, this represents the first large, multicenter study to address the effects of a leukotriene receptor antagonist in children younger than 5 years of age with persistent asthma, as well as one of the few asthma studies that incorporated end points validated for use in preschool children.Objective. Our primary objective was to determine the safety profile of montelukast, an oral leukotriene receptor antagonist, in preschool children with persistent asthma. Secondarily, the effect of montelukast on exploratory measures of asthma control was also studied.Design and Statistical Analysis. We conducted a double-blind, multicenter, multinational study at 93 centers worldwide: including 56 in the United States, and 21 in countries in Africa, Australia, Europe, North America, and South America. In this study, we randomly assigned 689 patients (aged 2-5 years) to 12 weeks of treatment with placebo (228 patients) or 4 mg of montelukast as a chewable tablet (461 patients) after a 2-week placebo baseline period. Patients had a history of physician-diagnosed asthma requiring use of ␤-agonist and a predefined level of daytime asthma symptoms. Caregivers answered questions twice daily on a validated, asthmaspecific diary card and, at specified times during the study, completed a validated asthma-specific quality-oflife questionnaire. Physicians and caregivers completed a global evaluation of asthma control at the end of the study.Efficacy end points included: daytime and overnight asthma symptoms, daily use of ␤-agonist, days without asthma, frequency of asthma attacks, number of patients discontinued because of asthma, need for rescue medication, physician and caregiver global evaluations of change, asthma-specific caregiver quality of life, and peripheral blood eosinophil counts. Although exploratory, the efficacy end points were predefined and their analyses were written in a data analysis plan before study unblinding. At screening and at study completion, a complete physical examination was performed. Routine laboratory tests were drawn at screening and weeks 6 and 12, and submitted to a central laboratory for a...

Leukotriene Modifier Therapy for Mild Sleep-disordered Breathing in Children

“…Montelukast is an orally bioavailable cysteinyl leukotriene (LT) receptor antagonist that is effective, safe, well tolerated, and approved by the U.S. Food and Drug Administration for preventive therapy for the inflammatory component in asthma and allergic rhinitis in children 2 years and older (21)(22)(23)(24), with no demonstrable development of tolerance in long-term studies (25,26). We have recently found that the cloned human cysteinyl LT receptors 1 and 2 (LT1-R, LT2-R) (27,28) have increased expression in the tonsillar tissues of children with SA (29).…”

Antileucotrienos no tratamento da asma e rinite alérgica

“…26 Spahn et al 17 have recently confirmed the effects of montelukast on peripheral airway obstruction and the concentration of eosinophilic cationic protein in children and adolescents with moderate asthma.…”

Understanding mild asthma/episodic asthma in children

“…A 12-week, multicentre, randomized, placebo-controlled, double-blind, parallel-group study was conducted to evaluate the clinical safety and efficacy of oral montelukast in 689 children 2 to 5 years of age with chronic asthma. 11 Montelukast significantly improved each of the components of the composite symptom score over 12 weeks of treatment. For example reduction in activity limitation scores were 40% versus 22% (p<0.001).…”

“…11 There improved compliance and safety make these agents seem attractive as alternatives for ICS in young children with mild persistent asthma. They also provide an alternative to long-acting β 2 -agonists as add on therapy.…”