title: Combination therapy with a long-acting beta-agonist and a leukotriene antagonist in moderate asthma.
abstract: BACKGROUND
  Long-acting beta-agonists (LABAs) and inhaled corticosteroids administered together appear to be complementary in terms of effects on asthma control. The elements of asthma control achieved by LABAs (improved lung function) and leukotriene receptor antagonists (LTRAs; protection against exacerbations) may be complementary as well.
  
  
  OBJECTIVE
  We sought to determine whether the combination of the LTRA montelukast and the LABA salmeterol could provide an effective therapeutic strategy for asthma.
  
  
  METHODS
  In a randomized, placebo-controlled, crossover study of 192 subjects with moderate asthma, we compared the clinical efficacy of regular treatment over 14 weeks with the combination of montelukast and salmeterol to that with the combination of beclomethasone and salmeterol in moderate asthma. The primary efficacy outcome was time to treatment failure.
  
  
  RESULTS
  Three months after the randomization of the last subject, the Data and Safety Monitoring Board determined that the primary research question had been answered and terminated the trial. The combination of montelukast and salmeterol was inferior to the combination of beclomethasone and salmeterol as judged by protection against asthma treatment failures (p = 0.0008), lung function (26 L/min difference in a.m. peak expiratory flow rate, p = 0.011), asthma control score (0.22 difference in Asthma Control Questionnaire score, p = 0.038), and markers of inflammation and airway reactivity.
  
  
  CONCLUSIONS
  Patients with moderate asthma similar to those we studied should not substitute the combination of an LTRA and an LABA for the combination of inhaled corticosteroid and an LABA.
authors.affiliation: Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. Aaron.Deykin@biogenidec.com
authors.forename: Aaron
authors.initials: A
authors.lastname: Deykin
authors.forename: Michael E
authors.initials: ME
authors.lastname: Wechsler
authors.forename: Homer A
authors.initials: HA
authors.lastname: Boushey
authors.forename: Vernon M
authors.initials: VM
authors.lastname: Chinchilli
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Kunselman
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Craig
authors.forename: Emily
authors.initials: E
authors.lastname: DiMango
authors.forename: John V
authors.initials: JV
authors.lastname: Fahy
authors.forename: Monica
authors.initials: M
authors.lastname: Kraft
authors.forename: Frank
authors.initials: F
authors.lastname: Leone
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Lazarus
authors.forename: Robert F
authors.initials: RF
authors.lastname: Lemanske
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.forename: Gene R
authors.initials: GR
authors.lastname: Pesola
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Peters
authors.forename: Christine A
authors.initials: CA
authors.lastname: Sorkness
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Szefler
authors.forename: Elliot
authors.initials: E
authors.lastname: Israel
mesh_terms: D000085:Acetates / Q000627:therapeutic use*; D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D003131:Combined Modality Therapy; D003521:Cyclopropanes; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011804:Quinolines / Q000627:therapeutic use*; D000068299:Salmeterol Xinafoate; D013440:Sulfides; D016896:Treatment Outcome
chemical_list: D000085:Acetates; D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D010919:Placebos; D011804:Quinolines; D013440:Sulfides; D000068299:Salmeterol Xinafoate; C093875:montelukast; D000420:Albuterol