Fluticasone/formoterol combination therapy is as effective as fluticasone/salmeterol in the treatment of asthma, but has a more rapid onset of action: an open-label, randomized study

Abstract

Background: The inhaled corticosteroid (ICS) fluticasone propionate (fluticasone) and the long-acting β2-agonist (LABA) formoterol fumarate (formoterol) are being made available as a combination product (fluticasone/formoterol, flutiform ®) in a single aerosol inhaler. This 12-week, open-label, randomized, active-controlled, parallel-group, multicentre, phase 3 study compared the efficacy and safety of fluticasone/formoterol with the commercially available combination product fluticasone/salmeterol.

Methods: Patients aged ≥ 18 years (N = 202) with mild-to-moderate-severe, persistent asthma for ≥ 6 months prior to screening were included in the study. After a screening phase (4-10 days), eligible patients were randomized 1:1 to receive fluticasone/formoterol or fluticasone/salmeterol during the 12-week treatment period. The primary objective was to demonstrate non-inferiority of fluticasone/formoterol versus fluticasone/salmeterol, measured by pre-dose forced expiratory volume in the first second (FEV1), at week 12.

Results: Fluticasone/formoterol was comparable to fluticasone/salmeterol for the primary efficacy endpoint, mean pre-dose FEV1 at week 12. The new combination was also comparable to fluticasone/salmeterol for change from baseline to week 12 in pre-dose FEV1, change from pre-dose FEV1 at baseline to 2-hour post-dose FEV1 at week 12 and discontinuations due to lack of efficacy. Importantly, fluticasone/formoterol was superior to fluticasone/salmeterol in time to onset of action throughout the duration of the study. The two treatments demonstrated similar results for various other secondary efficacy parameters, including other lung function tests, patient-reported outcomes, rescue medication use, asthma exacerbations and Asthma Quality of Life Questionnaire scores. Fluticasone/formoterol was well tolerated and had a good safety profile that was similar to fluticasone/salmeterol.

Conclusions: The results of this study indicate that fluticasone/formoterol is as effective as fluticasone/salmeterol, and has a more rapid onset of action, reflecting the faster bronchodilatory effects of formoterol compared with those of salmeterol. If patients perceive the benefits of therapy with fluticasone/formoterol more rapidly than with fluticasone/salmeterol, this could have a positive impact on preference and adherence.

Trial registration: ClinicalTrials.gov NCT00476073.

Figure 1

Participant flow.

Figure 2

Mean (± 95% CI) pre-dose FEV₁ throughout treatment. Data shown for per protocol population. Least-squares mean of the treatment difference at week 12: –0.061 L; 95% CI: –0.161, 0.040; p = 0.007, demonstrating non-inferiority. CI, confidence interval; FEV₁, forced expiratory volume in the first second.

Figure 3

Time to onset of action of study medication at baseline (day 0; similar plots were obtained at weeks 2, 6 and 12). Data based on Kaplan-Meier survival analysis (full analysis set). Onset of action was defined as the first time point post-dose at which FEV₁ was at least 12% greater than the pre-dose value. Analysis of time to onset of action using the multiple failures time model showed superiority of fluticasone/formoterol over fluticasone/salmeterol (hazard ratio: 1.64; 95% CI: 1.28, 2.10; p < 0.001). On day 0, more than twice as many patients had a bronchodilatory response that met the onset of action criterion in the fluticasone/formoterol group than in the fluticasone/salmeterol group at 5 minutes post-dose (39% versus 14%, respectively). In addition, a larger proportion of patients in the fluticasone/formoterol group met the onset of action criteria within 2 hours (post-dose), than in the fluticasone/salmeterol group (77% versus 64%, respectively; day 0). This trend continued over the 12-week treatment period, with consistently more patients achieving the predefined onset of action response in the fluticasone/formoterol group than in the fluticasone/salmeterol group at each post-dose time point (5–120 minutes). CI, confidence interval; FEV₁, forced expiratory volume in the first second.