title: A Randomized Pragmatic Trial of Changing to and Stepping Down Fluticasone/Formoterol in Asthma.
abstract: BACKGROUND
  Guidelines recommend reducing treatment in patients with well-controlled asthma after 3 months of stability. However, there is inadequate real-life data to guide physicians on therapy change in daily practice.
  
  
  OBJECTIVE
  To assess asthma control after change to and step-down of fluticasone propionate/formoterol fumarate dihydrate (FP/FOR) in real-life patients.
  
  
  METHODS
  In a randomized controlled, pragmatic, open-label trial, 225 well-controlled patients with asthma were randomized (1:2) to maintain high-dose fluticasone propionate/salmeterol xinafoate (FP/SAL, 1000/100 μg) or switch to FP/FOR (1000/40 μg) daily for 12 weeks (phase 1). One hundred sixteen patients stable on FP/FOR at week 12 were subsequently randomized (1:1) to maintain this therapy, or stepped down to FP/FOR (500/20 μg) daily for 12 weeks (phase 2). The primary end point was the 7-question Asthma Control Questionnaire (ACQ7) score.
  
  
  RESULTS
  In phase 1, FP/FOR (1000/40 μg) (n = 126) was noninferior to FP/SAL (1000/100 μg) (n = 73) for ACQ7 (difference in means, -0.12; 95% CI, -0.32 to 0.09). In phase 2, FP/FOR (500/20 μg) (n = 52) was noninferior to FP/FOR (1000/40 μg) (n = 52) for ACQ7 (difference in means, 0.01; 95% CI, -0.20 to 0.22). There was no significant difference in exacerbation rate between the groups in either phase. However, 1 to 2 exacerbations in 12 months before phase 1 were associated with the occurrence of an exacerbation after step-down (P = .007).
  
  
  CONCLUSIONS
  In patients with well-controlled asthma, a change from FP/SAL to FP/FOR did not compromise asthma control. Step-down of FP/FOR was well tolerated; however, in contrast to current guidelines, our data suggest caution in stepping down patients uncontrolled in the last 12 months. Larger step-down studies are required to confirm these findings.
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, United Kingdom; Royal Brompton Hospital, London, United Kingdom.
authors.forename: Omar S
authors.initials: OS
authors.lastname: Usmani
authors.affiliation: Research in Real Life Ltd, Cambridge, United Kingdom; Optimum Patient Care Global Ltd, Cambridge, United Kingdom.
authors.forename: Anu
authors.initials: A
authors.lastname: Kemppinen
authors.affiliation: Cambridge Research Support Ltd, Cambridge, United Kingdom.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Gardener
authors.affiliation: Cambridge Research Support Ltd, Cambridge, United Kingdom.
authors.forename: Vicky
authors.initials: V
authors.lastname: Thomas
authors.affiliation: Cambridge Research Support Ltd, Cambridge, United Kingdom.
authors.forename: Priyanka Raju
authors.initials: PR
authors.lastname: Konduru
authors.affiliation: Research in Real Life Ltd, Cambridge, United Kingdom; Optimum Patient Care Global Ltd, Cambridge, United Kingdom.
authors.forename: Christina
authors.initials: C
authors.lastname: Callan
authors.affiliation: Research in Real Life Ltd, Cambridge, United Kingdom; Optimum Patient Care Global Ltd, Cambridge, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: McLoughlin
authors.affiliation: Research in Real Life Ltd, Cambridge, United Kingdom; Optimum Patient Care Global Ltd, Cambridge, United Kingdom.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Woodhead
authors.affiliation: Optimum Patient Care, Cambridge, United Kingdom.
authors.forename: Adam
authors.initials: A
authors.lastname: Brady
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Elizabeth F
authors.initials: EF
authors.lastname: Juniper
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, United Kingdom; Royal Brompton Hospital, London, United Kingdom.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Barnes
authors.affiliation: Research in Real Life Ltd, Cambridge, United Kingdom; Academic Primary Care, University of Aberdeen, Aberdeen, United Kingdom; Observational and Pragmatic Research Institute, Singapore. Electronic address: dprice@opri.sg.
authors.forename: David
authors.initials: D
authors.lastname: Price
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D002985:Clinical Protocols; D004338:Drug Combinations; D005260:Female; D000068298:Fluticasone / Q000627:therapeutic use*; D000068759:Formoterol Fumarate / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D000068299:Salmeterol Xinafoate / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D001993:Bronchodilator Agents; D004338:Drug Combinations; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000068759:Formoterol Fumarate
keywords: ACQ7; Antiasthmatic agents; Biomarkers; Combination therapy; Fluticasone; Formoterol; Fractional exhaled nitric oxide; Inhaled corticosteroids; Pragmatic trials; Salmeterol; Step-down