title: Leukotriene antagonists as first-line or add-on asthma-controller therapy.
abstract: BACKGROUND
  Most randomized trials of treatment for asthma study highly selected patients under idealized conditions.
  
  
  METHODS
  We conducted two parallel, multicenter, pragmatic trials to evaluate the real-world effectiveness of a leukotriene-receptor antagonist (LTRA) as compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta(2)-agonist (LABA) as add-on therapy in patients already receiving inhaled glucocorticoid therapy. Eligible primary care patients 12 to 80 years of age had impaired asthma-related quality of life (Mini Asthma Quality of Life Questionnaire [MiniAQLQ] score ≤6) or inadequate asthma control (Asthma Control Questionnaire [ACQ] score ≥1). We randomly assigned patients to 2 years of open-label therapy, under the care of their usual physician, with LTRA (148 patients) or an inhaled glucocorticoid (158 patients) in the first-line controller therapy trial and LTRA (170 patients) or LABA (182 patients) added to an inhaled glucocorticoid in the add-on therapy trial.
  
  
  RESULTS
  Mean MiniAQLQ scores increased by 0.8 to 1.0 point over a period of 2 years in both trials. At 2 months, differences in the MiniAQLQ scores between the two treatment groups met our definition of equivalence (95% confidence interval [CI] for an adjusted mean difference, -0.3 to 0.3). At 2 years, mean MiniAQLQ scores approached equivalence, with an adjusted mean difference between treatment groups of -0.11 (95% CI, -0.35 to 0.13) in the first-line controller therapy trial and of -0.11 (95% CI, -0.32 to 0.11) in the add-on therapy trial. Exacerbation rates and ACQ scores did not differ significantly between the two groups.
  
  
  CONCLUSIONS
  Study results at 2 months suggest that LTRA was equivalent to an inhaled glucocorticoid as first-line controller therapy and to LABA as add-on therapy for diverse primary care patients. Equivalence was not proved at 2 years. The interpretation of results of pragmatic research may be limited by the crossover between treatment groups and lack of a placebo group. (Funded by the National Coordinating Centre for Health Technology Assessment U.K. and others; Controlled Clinical Trials number, ISRCTN99132811.).
authors.affiliation: Centre of Academic Primary Care, University of Aberdeen, Aberdeen, United Kingdom. david@rirl.org
authors.forename: David
authors.initials: D
authors.lastname: Price
authors.forename: Stanley D
authors.initials: SD
authors.lastname: Musgrave
authors.forename: Lee
authors.initials: L
authors.lastname: Shepstone
authors.forename: Elizabeth V
authors.initials: EV
authors.lastname: Hillyer
authors.forename: Erika J
authors.initials: EJ
authors.lastname: Sims
authors.forename: Richard F T
authors.initials: RF
authors.lastname: Gilbert
authors.forename: Elizabeth F
authors.initials: EF
authors.lastname: Juniper
authors.forename: Jon G
authors.initials: JG
authors.lastname: Ayres
authors.forename: Linda
authors.initials: L
authors.lastname: Kemp
authors.forename: Annie
authors.initials: A
authors.lastname: Blyth
authors.forename: Edward C F
authors.initials: EC
authors.lastname: Wilson
authors.forename: Stephanie
authors.initials: S
authors.lastname: Wolfe
authors.forename: Daryl
authors.initials: D
authors.lastname: Freeman
authors.forename: H Miranda
authors.initials: HM
authors.lastname: Mugford
authors.forename: Jamie
authors.initials: J
authors.lastname: Murdoch
authors.forename: Ian
authors.initials: I
authors.lastname: Harvey
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D011795:Surveys and Questionnaires; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D005938:Glucocorticoids; D020024:Leukotriene Antagonists