AB038. Pragmatic trial comparing continuing Seretide^® MDI with changing to Flutiform^® in asthma

Background: Selecting the most appropriate asthma therapy for individual patients can be challenging owing to limited data on real-life effectiveness of inhaled corticosteroid (ICS)/long-acting beta2-agonist (LABA) combinations available. Various factors, such as ease of use of the device and speed of onset of the LABA, can influence inhaler technique and adherence, thereby affecting clinical outcomes in real-life patients. Further studies are needed to evaluate whether efficacy of new asthma therapies demonstrated in clinical trials translate to effectiveness in a pragmatic setting.To compare the real-life effectiveness of switching to Flutiform^® 250 (250 mcg fluticasone/10 mcg formoterol) from Seretide^® 250 Evohaler^® (250 mcg fluticasone/25 mcg salmeterol) in adult patients with asthma.

Methods: This was the first phase of a pragmatic, open label, randomised controlled, non-inferiority trial in adult patients with asthma. Key eligibility criteria included prescription for Seretide^® 250 Evohaler^® for at least 6 months and no asthma exacerbations in the 3 months prior to enrolment. In addition, at the baseline visit, patients had to demonstrate controlled or partially controlled asthma according to Global Initiative for Asthma (GINA) criteria. Overall, 225 patients from 27 sites in the UK were randomised 2:1 to Flutiform^® 250 or Seretide^® 250 Evohaler^® for 12 weeks. 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 during the follow-up period. Secondary outcomes included the Mini-Asthma Quality of Life Questionnaire (Mini-AQLQ), Forced Expiratory Volume in 1 second (FEV1) % predicted, perception of asthma symptoms assessed with a Visual Analog Scale (VAS), asthma control (GINA) and absence of exacerbations during outcome period. Analyses of secondary outcomes included all randomised patients [Full Analysis Set (FAS)].

Results: Of the 207 patients who completed the study 90 (43%) were male, the mean (standard deviation) age was 53 (13) years, and 152 (73%) had not had an exacerbation in the year prior to the study. Of those randomised to Flutiform^® 250 126 (83%) were eligible for the non-inferiority analysis compared to 73 (99%) randomised to Seretide^® 250 Evohaler^® (see figure for details of the FAS). At Week 12, Flutiform^® 250 was non-inferior to Seretide^® 250 Evohaler^® in terms of asthma control assessed by ACQ7 with an upper confidence limit of 0.09, which is less than the pre-defined limit of 0.3 [mean difference −0.11; 95% confidence interval (CI), −0.31 to 0.09]. The odds of being more controlled according to GINA criteria were significantly higher in the Flutiform^® 250 group (odds ratio 2.04; 95% CI, 1.16 to 3.59; P=0.01). No significant differences between the groups were found for exacerbations, Mini-AQLQ, VAS or FEV1% predicted (see table). Although there was no significant difference in the distribution of adherence between the groups (P=0.51 using Fisher’s Exact Test), a greater proportion of patients in the Flutiform^® 250 group had adherence of 100% or more [34 (33%) compared with 13 (24%)].

Conclusions: Real-life patients previously controlled on Seretide^® 250 Evohaler^® can be switched to Flutiform^® 250 and maintain good asthma control. Moreover, patients on Flutiform^® 250 were significantly better controlled than patients on Seretide^® 250 Evohaler^® when asthma control was assessed according to GINA criteria.

Keywords: Asthma; therapy; inhaled corticosteroid (ICS); long-acting beta2-agonist (LABA); effectiveness