title: Dose-dependent anti-inflammatory effect of inhaled mometasone furoate/formoterol in subjects with asthma.
abstract: OBJECTIVE
  A well-controlled study in patients with allergic asthma was warranted to assess dose-dependency between fractional concentration of exhaled nitric oxide (FeNO) and sputum eosinophils to a combination of an inhaled corticosteroid plus a long-acting β2-agonist. We sought to characterize the dose-dependency of mometasone furoate/formoterol (MF/F) using FeNO and sputum eosinophil percentage as surrogates of airway inflammation in subjects with allergic asthma.
  
  
  METHODS
  Following a 2-week, open-label run-in, 93 subjects (≥12 y) using only short-acting beta agonist reliever medication as needed, were randomized to twice daily (BID) placebo; MF/F 100/10 μg, 200/10 μg, or 400/10 μg (via pressurized metered-dose inhaler [MDI]); MF-MDI 200 μg; or MF 200 μg via dry powder inhaler (DPI) during a 2-week, double-blind treatment period.
  
  
  RESULTS
  All active treatments demonstrated significant percentage reductions from baseline in FeNO compared with placebo at all time points (P ≤ 0.034). At endpoint, mean MF/F treatment group FeNO reductions ranged from -35.3% to -61.4%. Sputum eosinophil percentage reductions from baseline were significant compared with placebo for the MF/F 200/10 μg, MF/F 400/10 μg, and MF-DPI 200 μg groups at endpoint (P ≤ 0.023). Escalating MF/F doses significantly reduced both FeNO (P ≤ 0.001) and sputum eosinophil (P ≤ 0.022) levels in a dose-dependent manner at all time points. All treatments were well tolerated; no serious adverse events were observed.
  
  
  CONCLUSIONS
  All 3 MF/F doses demonstrated pronounced, clinically meaningful, dose-dependent reductions in FeNO, with reduced sputum eosinophil levels for MF/F 200/10 μg and MF/F 400/10 μg. These findings suggest both inflammatory markers may be useful in assessing corticosteroid responsiveness in asthma patients, and perhaps identifying the same asthma subphenotype. Clinical Trials.gov: NCT00635882.
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ 08889, USA. hendrik.nolte@merck.com
authors.forename: Hendrik
authors.initials: H
authors.lastname: Nolte
authors.forename: Ian
authors.initials: I
authors.lastname: Pavord
authors.forename: Vibeke
authors.initials: V
authors.lastname: Backer
authors.forename: Sheldon
authors.initials: S
authors.lastname: Spector
authors.forename: Tulin
authors.initials: T
authors.lastname: Shekar
authors.forename: Davis
authors.initials: D
authors.lastname: Gates
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Nair
authors.forename: Frederick
authors.initials: F
authors.lastname: Hargreave
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001944:Breath Tests / Q000379:methods; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002940:Circadian Rhythm / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D004804:Eosinophils / Q000473:pathology; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D000068759:Formoterol Fumarate; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D000068656:Mometasone Furoate; D009569:Nitric Oxide / Q000378:metabolism; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D011244:Pregnadienediols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D013183:Sputum / Q000166:cytology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D005938:Glucocorticoids; D011244:Pregnadienediols; D000068656:Mometasone Furoate; D009569:Nitric Oxide; D000068759:Formoterol Fumarate