Pharmacotherapy--first-line maintenance therapy

• Published in: Canadian Medical Association journal (CMAJ) 2005-09, Vol.173 (6 Suppl), p.S28-S32
• Main Authors: Becker, Allan, Bérubé, Denis, Zave Chad, Dolovich, Myrna
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Adrenal Cortex Hormones - administration & dosage; Adrenal Cortex Hormones - therapeutic use; Adrenergic beta-Agonists - therapeutic use; Asthma - drug therapy; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Leukotriene Antagonists - administration & dosage; Leukotriene Antagonists - therapeutic use; Pediatrics - standards; Supplement
• ISSN: 0820-3946; 1488-2329
• DOI: 10.1503/cmaj.045064

Four randomized controlled trials examined the efficacy of LTRAs compared with placebo in the pediatric population.3-6 Among preschool-aged children, 2 randomized, double-blind, parallel trials compared montelukast to placebo. Knorr and colleagues3 studied 689 children, aged 2-5 years, with mild persistent asthma who received either montelukast, 4 mg once daily at bedtime, or placebo for 12 weeks. Most children had activity-induced asthma (79%), abnormal radio-allergosorbent test (RAST) (49%) or both. Montelukast or placebo was administered in addition to ICSs in 28% of patients, in addition to cromolyn in 12% and as monotherapy in the remainder. No subgroup analyses were provided to allow assessment of the efficacy of montelukast as monotherapy. Overall, when used either as an add-on or monotherapy, montelukast was found to be significantly more effective than placebo in terms of a number of outcomes, including days without asthma (64% v. 59%, p = 0.01); reduction in asthma symptoms (37% v. 26%, p = 0.003); days with β^sup 2^-agonist use (49% v. 55%, p = 0.001), use of rescue oral steroids (19% v. 28%, p = 0.008), but was not significantly more effective in reducing the number of patients with 1 or more exacerbation (26% v. 32%, p = 0.10). The number of patients who did not complete the study was similar in both groups (10% in the montelukast group; 11% in the placebo group). The effect of montelukast was evident within 1 day of starting therapy. Two randomized, placebo-controlled, parallel-group, double-blind trials addressed the efficacy of LTRA in school-aged children. Knorr and colleagues5 studied 336 children aged 6-14 years with mild-to-moderate asthma and an average FEV^sub 1^ of 72% of the predicted value. The overwhelming majority of the children had exercise-induced asthma (94%) or allergic rhinitis (92%). Montelukast (5 mg/day) or placebo was administered for 8 weeks as monornerapy in 74% of the children or in addition to ICSs in 36% of the children. Compared with placebo, montelukast is associated with significantly greater improvements in FEV^sub 1^ over the baseline measure (8.2% v. 3.6%, p < 0.001), reduction in the use of β^sub 2^-agonist (-0.6 v. -0.2 puffs/day), improved quality of life (symptoms, activity and emotions), reduction in serum eosinophils (-0.05 v. 0.01 10^sup 9^/L, p = 0.02), fewer days with an asthma exacerbation (20.6% v. 26.7%, p = 0.5) and fewer patients with an asthma exacerbation (84.8% v. 95.5%, p = 0.002). However,