Background Current treatments for acute asthma provide inadequate benefit for some patients. Intravenous montelukast may complement existent therapies. Objective To evaluate efficacy of intravenous ...montelukast as adjunctive therapy for acute asthma. Methods A total of 583 adults with acute asthma were treated with standard care during a ≤60-minute screening period. Patients with FEV1 ≤50% predicted were randomly allocated to intravenous montelukast 7 mg (n = 291) or placebo (n = 292) in addition to standard care. This double-blind treatment period lasted until a decision for discharge, hospital admission, or discontinuation from the study. The primary efficacy endpoint was the time-weighted average change in FEV1 during 60 minutes after drug administration. Secondary endpoints included the time-weighted average change in FEV1 at various intervals (10-120 minutes) and percentage of patients with treatment failure (defined as hospitalization or lack of decision to discharge by 3 hours postadministration). Results Montelukast significantly increased FEV1 at 60 minutes postdose; the difference between change from baseline for placebo (least-squares mean of 0.22 L; 95% CI, 0.17, 0.27) and montelukast (0.32 L; 95% CI, 0.27, 0.37) was 0.10 L (95% CI, 0.04, 0.16). Similar improvements in FEV1 -related variables were seen at all time points (all P <.05). Although treatment failure did not differ between groups (OR 0.92; 95% CI, 0.63, 1.34), a prespecified subgroup analysis suggests likely benefit for intravenous montelukast at US sites. Conclusion Intravenous montelukast added to standard care in adults with acute asthma produced significant relief of airway obstruction throughout the 2 hours after administration, with an onset of action as early as 10 minutes.
Background Prostaglandin D2 is a proinflammatory mediator believed to be important in asthma and allergic rhinitis (AR). Allelic variants in the prostaglandin D2 receptor type 1 (DP1) gene (PTGDR) ...have been suggested to be associated with asthma susceptibility. Objectives We sought to investigate the efficacy of the DP1 antagonist laropiprant (alone or with montelukast) in asthma and seasonal AR and explore whether sequence variations in PTGDR are associated with asthma severity. Methods For asthma, in a double-blind crossover study, 100 patients with persistent asthma were randomized to placebo or laropiprant, 300 mg/d for 3 weeks, followed by addition of montelukast, 10 mg/d for 2 weeks. PTGDR promoter haplotypes were categorized as high, medium, or low transcriptional efficiency. The primary efficacy end point was FEV1 . For AR, in a double-blind parallel-group study, 767 patients sensitized to a regionally prevalent fall allergen with symptomatic fall rhinitis were allocated to laropiprant, 25 mg/d or 100 mg/d; cetirizine, 10mg/d; or placebo for 2 weeks. The primary end point was the Daytime Nasal Symptoms Score. Results For asthma, no significant differences in FEV1 or asthma symptoms were noted for laropiprant versus placebo or laropiprant plus montelukast vs montelukast (differences between montelukast and placebo: P ≤ .001). No clear association was seen between haplotype pair (ie, diplotype) and asthma severity. For AR, although cetirizine (vs placebo) demonstrated an improvement in the Daytime Nasal Symptoms Score ( P < .001), laropiprant did not. Conclusion Laropiprant did not demonstrate efficacy in asthmatic patients or patients with AR. Variations in PTGDR did not appear related to baseline asthma severity or treatment response (NCT00533208; NCT00783601).
Abstract Background: Asthma is a chronic disease with a heterogeneous phenotype that is often associated with allergic sensitization in childhood. The earliest definable form of asthma is mild ...(intermittent or persistent), a severity level that may be characteristic of a majority of children with asthma. Several asthma controllers are indicated for use in children. International guidelines recommend the use of inhaled corticosteroids as the preferred controller therapy in mild persistent asthma. Objective: This article reviewed recent results from randomized, double-blind studies of children with mild asthma treated with montelukast, a leukotriene receptor antagonist that is approved for the treatment of asthma and allergic rhinitis in children and adults. Methods: A literature search of MEDLINE was conducted to gather relevant, English-language articles using search terms such as randomized controlled studies, double-blind studies, montelukast, leukotriene receptor antagonist, pediatric asthma, mild asthma, exercise-induced asthma, and bronchoconstriction. Recent articles (since 1998) that described the use of montelukast as a monotherapy were chosen for this review. Results: Releevant studies included a 48-week, placebo-controlled study of 2- to 5-year-old mild intermittent asthmatics (N = 549); a 12-week, placebo-controlled study of 2- to 5-year-old mild persistent asthmatics (N = 689); an analysis of a mild persistent asthmatic cohort (N = 138) from an 8-week, placebo-controlled study of 6- to 14-year-old asthmatics; a 12-month study comparing montelukast with fluticasone in 6- to 14-year-old mild persistent asthmatics (N = 949); and 3 placebo-controlled studies in children with exercise-induced asthma (N = 123). The results from these studies, encompassing end points measuring lung function and symptoms, found that montelukast provided effective and beneficial asthma control to children aged 2 to 14 years with mild asthma. Conclusion: The evidence suggests that montelukast is an effective monotherapy controller in children with mild asthma.
