title: The efficacy and tolerability of inhaled montelukast plus inhaled mometasone compared with mometasone alone in patients with chronic asthma.
abstract: BACKGROUND
  The efficacy of oral montelukast in chronic asthma is well established. Montelukast is also an effective adjunctive therapy to inhaled corticosteroids (ICS) in asthma uncontrolled on ICS alone. Inhaled montelukast was recently shown to provide significant bronchodilation compared with placebo in patients with chronic asthma. The purpose of this study was to evaluate the efficacy of inhaled montelukast added to inhaled mometasone.
  
  
  METHODS
  This was an 8-week, multicenter, randomized, double-blind, placebo-controlled study comparing once-daily inhaled montelukast 1 mg plus inhaled mometasone 220 μg (delivered by separate dry powder inhalers) with placebo plus inhaled mometasone 220 μg. Men and women aged 15-85 years with chronic asthma, forced expiratory volume in 1 second (FEV(1)) 50-80% of the predicted value, and β-agonist reversibility ≥12% were eligible. Patients were required to meet a minimum symptom threshold while receiving open-label inhaled mometasone during a 3-week prestudy/run-in period. Patients received blinded (montelukast vs. placebo) treatment for 2 weeks, entered a 1-week washout period, then crossed over to the other treatment for 2 weeks. The primary endpoint was the average change from baseline in FEV(1) over the 2-week treatment period. Secondary endpoints included daytime and nighttime symptom scores. Other endpoints included short-acting β-agonist (SABA) use, asthma exacerbations, asthma control, peak expiratory flow (PEF), and blood eosinophil count.
  
  
  RESULTS
  A total of 134 patients were randomized. For the primary endpoint, change from baseline in FEV(1), inhaled montelukast plus inhaled mometasone was significantly more effective than placebo plus inhaled mometasone (least squares mean 0.22 L vs. 0.17 L; p = .033 [two-sided at α = 0.05]). Inhaled montelukast plus inhaled mometasone was also significantly more effective than placebo plus inhaled mometasone in improving daytime asthma symptom scores (p = .005) and nighttime asthma symptom scores (p = .015), increasing the percentage of days with asthma control (p = .004), decreasing the percentage of days with asthma exacerbations (p ≤ .001), and decreasing the blood eosinophil count (p = .013). Differences were not significant on AM or PM PEF or SABA use, although the latter approached significance (p = .073). Both treatments were well tolerated.
  
  
  CONCLUSIONS
  Inhaled montelukast plus inhaled mometasone was significantly more effective than placebo plus inhaled mometasone in improving FEV(1), symptoms, asthma control, and blood eosinophil count.
authors.affiliation: Clinical Research, Merck & Co., Inc., Whitehouse Station, NJ 19454, USA. george_philip@merck.com
authors.forename: George
authors.initials: G
authors.lastname: Philip
authors.forename: César
authors.initials: C
authors.lastname: Villarán
authors.forename: Shailen R
authors.initials: SR
authors.lastname: Shah
authors.forename: Kristel
authors.initials: K
authors.lastname: Vandormael
authors.forename: Steven S
authors.initials: SS
authors.lastname: Smugar
authors.forename: Theodore F
authors.initials: TF
authors.lastname: Reiss
mesh_terms: D000085:Acetates / Q000008:administration & dosage* / Q000009:adverse effects; D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy*; D002908:Chronic Disease; D016001:Confidence Intervals; D018592:Cross-Over Studies; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D016014:Linear Models; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D000068656:Mometasone Furoate; D010349:Patient Compliance; D011244:Pregnadienediols / Q000008:administration & dosage* / Q000009:adverse effects; D011804:Quinolines / Q000008:administration & dosage* / Q000009:adverse effects; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D013147:Spirometry; D013440:Sulfides; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D000085:Acetates; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D003521:Cyclopropanes; D011244:Pregnadienediols; D011804:Quinolines; D013440:Sulfides; D000068656:Mometasone Furoate; C093875:montelukast