title: Tiotropium is noninferior to salmeterol in maintaining improved lung function in B16-Arg/Arg patients with asthma.
abstract: BACKGROUND
  The efficacy and safety of inhaled long-acting β(2)-adrenergic agonists in asthmatic patients with the B16-Arg/Arg genotype has been questioned, and the use of antimuscarinics has been proposed as an alternative in patients whose symptoms are not controlled by inhaled corticosteroids (ICSs).
  
  
  OBJECTIVE
  We compared the efficacy and safety of the long-acting anticholinergic tiotropium with salmeterol and placebo added to an ICS in B16-Arg/Arg patients with asthma that was not controlled by ICSs alone.
  
  
  METHODS
  In a double-blind, double-dummy, placebo-controlled trial, after a 4-week run-in period with 50 μg of twice-daily salmeterol administered through a metered-dose inhaler, 388 asthmatic patients were randomized 1:1:1 to 16 weeks of treatment with 5 μg of Respimat tiotropium administered daily in the evening, 50 μg of salmeterol administered twice daily through a metered-dose inhaler, or placebo. Patients aged 18 to 67 years demonstrated reversibility to bronchodilators, and their symptoms were uncontrolled by regular ICSs (400-1000 μg of budesonide/equivalent). ICS regimens were maintained throughout the trial. The mean weekly morning peak expiratory flow (PEF) before randomization was 358 ± 115.7 L/min (range, 80.3-733.0 L/min).
  
  
  RESULTS
  Changes in weekly PEF from the last week of the run-in period to the last week of treatment (primary end point: change in PEF) were -3.9 ± 4.87 L/min (n = 128) for tiotropium and -3.2 ± 4.64 L/min (n = 134) for salmeterol, and these were superior to placebo (-24.6 ± 4.84 L/min, n = 125, P < .05). Tiotropium was noninferior to salmeterol (estimated difference, -0.78 L/min [95% CI, -13.096 to 11.53]; P = .002; α = .025, 1-sided; noninferiority, 20 L/min). Tiotropium and salmeterol were numerically superior to placebo in some patient-reported secondary outcomes. Adverse events were comparable across treatments.
  
  
  CONCLUSIONS
  Tiotropium was more effective than placebo and as effective as salmeterol in maintaining improved lung function in B16-Arg/Arg patients with moderate persistent asthma. Safety profiles were comparable.
authors.affiliation: Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Bateman
authors.forename: Oliver
authors.initials: O
authors.lastname: Kornmann
authors.forename: Peter
authors.initials: P
authors.lastname: Schmidt
authors.forename: Anna
authors.initials: A
authors.lastname: Pivovarova
authors.forename: Michael
authors.initials: M
authors.lastname: Engel
authors.forename: Leonardo M
authors.initials: LM
authors.lastname: Fabbri
mesh_terms: D000280:Administration, Inhalation; D000420:Albuterol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001120:Arginine / Q000235:genetics*; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010366:Peak Expiratory Flow Rate; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012129:Respiratory Function Tests; D000068299:Salmeterol Xinafoate; D012602:Scopolamine Derivatives / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069447:Tiotropium Bromide; D016896:Treatment Outcome
chemical_list: C553443:ADRB2 protein, human; D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2; D012602:Scopolamine Derivatives; D000068299:Salmeterol Xinafoate; D001120:Arginine; D000420:Albuterol; D000069447:Tiotropium Bromide