AB039. Pragmatic trial stepping down Flutiform in patients maintained on high dose ICS
Poster Session

AB039. Pragmatic trial stepping down Flutiform® in patients maintained on high dose ICS

Anu Kemppinen1, Elizabeth Gardener2, Vicky Thomas2, Priyanka Raju2, Christina Callan1, Andrew McLoughlin1, Vanessa Woodhead1, Adam Brady3, Elizabeth F. Juniper4, Peter Barnes5, Omar S. Usmani5, David Price6,7

1Research in Real Life, Cambridge, UK; 2Cambridge Research Support Ltd, Cambridge, UK; 3Optimum Patient Care, Cambridge, UK; 4Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada; 5National Heart and Lung Institute, Imperial College London & Royal Brompton Hospital, London, UK; 6Academic Primary Care, University of Aberdeen, Aberdeen, UK; 7Observational and Pragmatic Research Institute, Singapore

Background: Global Initiative for Asthma (GINA) guidelines recommend a gradual step-down of asthma therapy if asthma has been well-controlled for at least 3 months. In real life, however, many well-controlled patients are prescribed high doses of inhaled corticosteroids (ICS), and are therefore unnecessarily at risk of systemic side effects associated with long-term ICS use. To encourage and facilitate step-down in a clinical setting, further pragmatic studies are required to demonstrate that good control of asthma can be maintained with a lower dose of ICS in stable and controlled patients, and to explore potential predictors for response to step-down.To test if good control of asthma can be maintained in adult patients previously stable on Flutiform® 250 (250 mcg fluticasone/10 mcg formoterol) for 12 weeks, after step-down to Flutiform® 125 (250 mcg fluticasone/5 mcg formoterol).

Methods: This was the second phase of a pragmatic, open-label, randomised controlled, non-inferiority trial in adult patients with asthma. Patients eligible for this phase had been on Flutiform® 250 for 12 weeks, had had no exacerbations during this period and were considered suitable for step-down by their GP. A total of 116 patients from 23 sites in the UK were randomised 1:1 to continue on Flutiform® 250 or to step down to Flutiform® 125. The primary outcome was asthma control assessed using the 7-item Asthma Control Questionnaire (ACQ7). Non-inferiority limit on the ACQ7 was set at 0.3. Patients were eligible for the non-inferiority analysis if they stayed on the randomised treatment for at least 8 weeks and did not change treatment before outcome visit. Secondary outcomes included forced expiratory volume in the first second (FEV1) % predicted, the Mini-Asthma Quality of Life Questionnaire (Mini-AQLQ), asthma control (according to GINA) and absence of exacerbations during outcome period. Analyses of secondary outcomes included all randomised patients [Full Analysis Set (FAS)]. Adherence was calculated based on dose counter values for patients who returned the study inhalers.

Results: Of the 107 patients who completed the study 48 (45%) were male and the mean [standard deviation (SD)] age was 54 (13) years. Of those randomised, 52 (90%) patients in each arm were eligible for the non-inferiority analysis (see figure for details of the FAS). At week 12, Flutiform® 125 was non-inferior to Flutiform® 250 in terms of asthma control assessed by ACQ7, with an upper confidence limit of 0.22, which is less than the pre-defined limit of 0.3 [mean difference 0.01; 95% confidence interval (CI), −0.20 to 0.22]. No significant differences between the groups were found for GINA asthma control, absence of exacerbations, Mini-AQLQ, or FEV1% predicted (see Table for treatment effect estimates). Adherence was high in both groups [median (inter-quartile range) 94% (88% to 106%) and 98% (77% to 103%) for the Flutiform® 125 and Flutiform® 250 groups, respectively] and there was no significant difference in distribution of adherence between the groups (P=0.20, Mann-Whitney U-test).

Conclusions: This study showed that real-life patients previously controlled on Flutiform® 250 can be stepped down to Flutiform® 125 and maintain good asthma control. Additional analyses are ongoing to investigate biomarkers [blood eosinophils, fractional exhaled nitric oxide (FeNO)] and other factors that might predispose patients to exacerbations or worsening of asthma control following ICS step-down. In the future, such predictors could help physicians to make more informed decisions on stepping down therapy in a real-life setting.

Keywords: Asthma; inhaled corticosteroids (ICS); flutiform

doi: 10.21037/jtd.2016.s039

Cite this abstract as: Kemppinen A, Gardener E, Thomas V, Raju P, Callan C, McLoughlin A, Woodhead V, Brady A, Juniper EF, Barnes P, Usmani OS, Price D. Pragmatic trial stepping down Flutiform® in patients maintained on high dose ICS. J Thorac Dis 2016;8(Suppl 5):AB039. doi: 10.21037/jtd.2016.s039

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