Peter Polos

Montelukast and fluticasone compared with salmeterol and fluticasone in protecting against asthma exacerbation in adults: one year, double blind, randomised, comparative trial

Abstract Objectives To assess the effect of montelukast versus salmeterol added to inhaled fluticasone propionate on asthma exacerbation in patients whose symptoms are inadequately controlled with fluticasone alone. Design and setting A 52 week, two period, double blind, multicentre trial during which patients whose symptoms remained uncontrolled by inhaled corticosteroids were randomised to add montelukast or salmeterol. Participants Patients (15-72 years; n = 1490) had a clinical history of chronic asthma for ≥ 1 year, a baseline forced expiratory volume in one second (FEV 1) value 50-90% predicted, and a β agonist improvement of ≥ 12% in FEV 1. Main outcome measures The primary end point was the percentage of patients with at least one asthma exacerbation. Results 20.1% of the patients in the group receiving montelukast and fluticasone had an asthma exacerbation compared with 19.1% in the group receiving salmeterol and fluticasone; the difference was 1% (95% confidence interval -3.1% to 5.0%). With a risk ratio (montelukast-fluticasone/salmeterol-fluticasone) of 1.05 (0.86 to 1.29), treatment with montelukast and fluticasone was shown to be non-inferior to treatment with salmeterol and fluticasone. Salmeterol and fluticasone significantly increased FEV 1 before a β agonist was used and morning peak expiratory flow compared with montelukast and fluticasone (P ≤ 0.001), whereas FEV 1 after a β agonist was used and improvements in asthma specific quality of life and nocturnal awakenings were similar between the groups. Montelukast and fluticasone significantly (P = 0.011) reduced peripheral blood eosinophil counts compared with salmeterol and fluticasone. Both treatments were generally well tolerated. Conclusion The addition of montelukast in patients whose symptoms remain uncontrolled by inhaled fluticasone could provide equivalent clinical control to salmeterol.

Montelukast, Compared With Fluticasone, for Control of Asthma Among 6- to 14-Year-Old Patients With Mild Asthma: The MOSAIC Study

Background. Guidelines recommend daily controller therapy for mild persistent asthma. Montelukast has demonstrated consistent benefit in controlling symptoms of asthma and may be an alternative, orally administered, nonsteroidal agent for treating mild asthma. Methods. The Montelukast Study of Asthma in Children (MOSAIC study) was a 12-month, multicenter, randomized, double-blind, noninferiority trial to determine the effect of once-daily, orally administered montelukast (5 mg) (n = 495), compared with twice-daily, inhaled fluticasone (100 μg) (n = 499), on the percentage of asthma rescue-free days (RFDs) (any day without asthma rescue medication and with no asthma-related resource use). Patients 6 to 14 years of age had mild persistent asthma (average percentage of predicted forced expiratory volume in 1 second: 87.2%; RFDs at baseline: 64%). Montelukast would be considered not inferior to fluticasone if the upper limit of the 95% confidence interval for the difference in mean percentages of RFDs (fluticasone minus montelukast) was above −7% (a difference of ∼2 days/month). Results. The mean percentage of RFDs was 84.0% in the montelukast group and 86.7% in the fluticasone group. The least-squares mean difference was −2.8% (95% confidence interval: −4.7% to −0.9%), within the noninferiority limit of −7%. The proportion of patients requiring systemic corticosteroids and the number of patients with an asthma attack were greater in the montelukast group. Both montelukast and fluticasone were well tolerated. Conclusions. Montelukast was demonstrated to be not inferior to fluticasone in increasing the percentage of RFDs among 6- to 14-year-old patients with mild asthma. Secondary end points, including percentage of predicted forced expiratory volume in 1 second value, days with β-receptor agonist use, and quality of life, improved in both groups but were significantly better in the fluticasone treatment group.

Effect of montelukast on lung function in asthma patients with allergic rhinitis: analysis from the COMPACT trial.

Background:  The Clinical Outcomes with Montelukast as a Partner Agent to Corticosteroid Therapy (COMPACT) trial demonstrated that montelukast added to budesonide (MNT + BD) was as efficacious as double the dose of budesonide (dBD) in improving morning peak expiratory flow (AM PEF) in adult asthmatics. Recent studies have demonstrated that montelukast is also effective in treating daytime and nighttime allergic rhinitis (AR) symptoms in asthmatic patients. This analysis was designed to examine whether asthmatic patients with comorbid AR respond differently than patients without comorbid AR in terms of asthma control (lung function).

Effect of montelukast or salmeterol added to inhaled fluticasone on exercise-induced bronchoconstriction in children

OBJECTIVES To evaluate the effect of montelukast, 5 mg, or inhaled salmeterol, 50 microg, added to inhaled fluticasone in reducing the maximum percentage decrease in forced expiratory volume in 1 second (FEV1) after a standardized exercise challenge and response to rescue bronchodilation with albuterol in children aged 6 to 14 years with persistent asthma and exercise-induced bronchoconstriction (EIB). METHODS Randomized, double-blind, double-dummy, multicenter, 2-period, 4-week, crossover study conducted between December 22, 2005 and November 14, 2008 at 30 centers in Europe, Asia, Mexico, and South America. Patients with asthma receiving inhaled corticosteroids demonstrated an FEV1 of 70% or higher of the predicted value and EIB (defined as a decrease in FEV1 > or = 15% compared with preexercise baseline FEV1 on 2 occasions before randomization). Standardized exercise challenges were performed at baseline (prerandomization) and at the end of each active treatment period. RESULTS Of 154 patients randomized, 145 completed the study. Montelukast, compared with salmeterol, significantly reduced the mean maximum percentage decrease in FEV1 (10.6% vs 13.8%; P = .009), mean area under the curve for the first 20 minutes after exercise (116.0% x min vs 168.8% x min; P = .006), and median time to recovery (6.0 vs 11.1 minutes; P = .04). Response to albuterol rescue after exercise challenge was significantly greater (P < .001) with montelukast. Montelukast and salmeterol were generally well tolerated. CONCLUSIONS Attenuation and response of EIB to albuterol rescue after exercise challenge were significantly better with montelukast than with salmeterol after 4 weeks of treatment.

The Efficacy of Montelukast during the Allergy Season in Pediatric Patients with Persistent Asthma and Seasonal Aeroallergen Sensitivity

Objective. To determine the effect of montelukast on asthma during the allergy season in children with persistent asthma and seasonal aeroallergen sensitivity. Design. This 3-week double-blind, placebo-controlled, parallel-group multicenter study compared daily montelukast 5 mg chewable tablets and placebo in patients 6–14 years of age with forced expiratory volume in 1 second (FEV1) ≥ 60 and ≤ 85% predicted, persistent asthma that is also active during allergy season, and documented sensitivity to seasonal allergens. Concomitant inhaled corticosteroid use was permitted in up to 40% of enrolled patients. The primary endpoint was the percentage change from baseline in FEV1 over 3 weeks of treatment. Additional endpoints included the percentage change from baseline in β -agonist use, average changes in daytime and nighttime symptom score, AM and PM peak expiratory flow rate (PEFR), investigators global asthma evaluation, and parent/guardian global asthma evaluation at the end of the treatment period. Adverse experiences (AEs) were collected to assess safety and tolerability. Results. A total of 421 patients were randomized to montelukast (N = 203) or placebo (N = 218). For the primary endpoint, the percentage change from baseline FEV1, montelukast was not significantly different from placebo (least squares mean 9.53% vs. 9.15%, respectively; p = 0.810). Compared with placebo, montelukast was associated with significantly lower (better) investigators global asthma evaluation (LS mean 2.71 vs. 2.98; p < 0.05) and parent/guardian global asthma evaluation (LS mean: 2.63 vs. 2.90; p < 0.05) scores. There were no significant differences between treatment groups for the other efficacy evaluations. Both treatments were well tolerated, with no significant differences observed in AE rates. Conclusion. Montelukast did not significantly improve FEV1 compared with placebo over three weeks of treatment during the allergy season in pediatric patients with seasonal allergen sensitivity. (ClinicalTrials.gov identifier: NCT00289874)