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

• DOI: 10.1542/peds.108.3.e48
• Publication Date: 2004-08-13T23:55:51Z
• Authors: Barbara Knorr; Luis M. Franchi; Hans Bisgaard; Jan Hendrik Verme...; Peter LeSouef; Nancy Santanello; Theresa M. Michele; Theodore F. Reiss; Ha H. Nguyen; Donna L. Bratton
• Keywords: Tolerability; Leukotriene receptor; Zafirlukast

Background. The greatest prevalence of asthma is in preschool children; however, the clinical utility therapy for this age group limited by a narrow therapeutic index, long-term tolerability, and frequency and/or difficulty administration. Inhaled corticosteroids inhaled cromolyn are most commonly prescribed controller therapies young children with persistent asthma, although very patients may have using inhalers, dose delivery can be variable. Moreover, reduced compliance relative to orally administered has been reported. One potential advantage montelukast ease administering once-daily chewable tablet; additionally, no tachyphylaxis or change safety profile evidenced after up 140 80 weeks adults pediatric aged 6 14 years, respectively. To our knowledge, represents first large, multicenter study address effects leukotriene receptor antagonist younger than 5 years as well one few studies that incorporated end points validated use children. Objective. Our primary objective was determine montelukast, an oral antagonist, asthma. Secondarily, effect on exploratory measures control also studied. Design Statistical Analysis. We conducted double-blind, multicenter, multinational at 93 centers worldwide: including 56 United States, 21 countries Africa, Australia, Europe, North America, South America. In study, we randomly assigned 689 (aged 2–5 years) 12 treatment placebo (228 patients) 4 mg tablet (461 2-week baseline period. Patients had history physician-diagnosed requiring β-agonist predefined level daytime symptoms. Caregivers answered questions twice daily validated, asthma-specific diary card and, specified times during completed quality-of-life questionnaire. Physicians caregivers global evaluation study. Efficacy included: overnight symptoms, β-agonist, days without attacks, number discontinued because need rescue medication, physician caregiver evaluations change, quality life, peripheral blood eosinophil counts. Although exploratory, efficacy were their analyses written data analysis plan before unblinding. At screening completion, complete physical examination performed. Routine laboratory tests drawn 12, submitted central analysis. Adverse collected from each clinic visit. An intention-to-treat approach, all measurement least 1 postrandomization measurement, performed points. analysis-of-variance model terms treatment, center stratum (inhaled/nebulized corticosteroid use, none) used estimate means between-group differences construct 95% confidence intervals. Treatment-by-age, -sex, -race, -radioallergosorbent test, -stratum, -study interactions evaluated term separately. Fisher's exact test comparisons discontinuations worsening frequencies adverse effects. Because imbalance values counts 2 groups, covariance patient's covariate. Study Participants. Of enrolled, approximately 60% boys white. relatively evenly divided age: 21%, 24%, 30%, 23% 2, 3, 4, For 77% patients, symptoms developed 3 life. During period, 6.1 days/week 6.0 days/week. Results. over 4-mg produced significant improvements compared multiple parameters including: (cough, wheeze, trouble breathing, activity limitation); (cough); percentage symptoms; asthma; corticosteroids; evaluations; eosinophils. benefit evident within day starting therapy. Improvements consistent across age, sex, race, center, whether not positive radioallergosorbent test. Montelukast demonstrated regardless concomitant inhaled/nebulized Caregiver evaluations, experiencing scores favored but significantly different placebo. There clinically meaningful between groups overall individual effects, exception which occurred more frequently group. elevated serum transaminase levels. Approximately 90% Conclusions. Oral (4-mg tablet) once effective generally tolerated important Similarly, improves control. Thus, confirms extends