A Randomized Pragmatic Trial of Changing to and Stepping Down Fluticasone/Formoterol in Asthma

J Allergy Clin Immunol Pract. 2017 Sep-Oct;5(5):1378-1387.e5. doi: 10.1016/j.jaip.2017.02.006. Epub 2017 Mar 25.


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.

Keywords: ACQ7; Antiasthmatic agents; Biomarkers; Combination therapy; Fluticasone; Formoterol; Fractional exhaled nitric oxide; Inhaled corticosteroids; Pragmatic trials; Salmeterol; Step-down.

Publication types

  • Pragmatic Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Asthma / drug therapy*
  • Bronchodilator Agents / therapeutic use*
  • Clinical Protocols
  • Drug Combinations
  • Female
  • Fluticasone / therapeutic use*
  • Formoterol Fumarate / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Practice Guidelines as Topic
  • Salmeterol Xinafoate / therapeutic use*
  • Surveys and Questionnaires
  • Treatment Outcome
  • Withholding Treatment


  • Bronchodilator Agents
  • Drug Combinations
  • Salmeterol Xinafoate
  • Fluticasone
  • Formoterol Fumarate