Use of concomitant inhaled corticosteroids: pooled data from two phase III studies of aclidinium plus formoterol in COPD

Abstract

Bronchodilator therapy is the backbone of the management of chronic obstructive pulmonary disease. In some patients, inhaled corticosteroids can be prescribed in combination with bronchodilators. Through a subgroup analysis of pooled data from two large phase III clinical trials of bronchodilator therapy according to concomitant inhaled corticosteroid use (user vs. non-user), we sought to evaluate the clinical benefit of adding inhaled corticosteroids to dual bronchodilator therapy in chronic obstructive pulmonary disease. The primary focus of this analysis of pooled data from the phase III ACLIFORM and AUGMENT studies was to evaluate the efficacy of aclidinium/formoterol on lung function stratified by inhaled corticosteroid use. We found that lung-function end points were significantly improved regardless of concomitant inhaled corticosteroid use among patients treated with the dual bronchodilator aclidinium/formoterol 400/12 µg twice daily compared with placebo and both monotherapies. Together with the previously reported observations that aclidinium/formoterol 400/12 µg reduces exacerbations vs. placebo in inhaled corticosteroid users and improves dyspnoea compared to monotherapy in inhaled corticosteroid non-users, these data suggest that both groups achieve lung function improvements, which translates to different clinical benefits depending on whether or not a patient is receiving concomitant inhaled corticosteroids.CHRONIC LUNG DISEASE: 'TRIPLE' THERAPY COULD PROVE BENEFICIAL: A dual bronchodilator therapy taken together with corticosteroid inhalers may benefit patients with severe chronic lung disease. Bronchodilator drugs relax the lungs and widen airways in patients with chronic obstructive pulmonary disease (COPD). While recent studies have shown that a dual bronchodilator therapy containing aclidinium and formoterol significantly improves lung function in COPD, little is known about combining the dual therapy with inhaled corticosteroids (ICSs). Anthony D'Urzo at the University of Toronto, Canada, and co-workers analysed data from 3394 patients with COPD undergoing dual therapy trials. Of these, 1180 were already taking ICSs. The team compared symptoms in the ICS group with those not taking ICSs. The dual therapy improved lung function across both groups regardless of ICS use, though patients gained different clinical benefits depending on ICS use and disease severity.

Fig. 1

LS mean change from baseline in 1-h morning post-dose FEV₁ vs. placebo at week 24 in ICS users a and non-ICS users b (pooled ITT population). ***P < 0.001 vs. placebo; ^††† P < 0.001 vs. aclidinium 400 μg; ^‡‡‡ P < 0.001 vs. formoterol 12 μg; ^§§§ P < 0.001 vs. aclidinium/formoterol 400/6 μg. Analyses based on the mixed model for repeated measures: treatment effects and treatment comparisons. Error bars represent 95% confidence intervals. Patient numbers for the placebo groups were: for patients using ICS, n = 137, for patients not using ICS, n = 251. FEV ₁ forced expiratory volume in 1 s, ICS inhaled corticosteroid, ITT intent-to-treat, LS least squares, mL millilitre

Fig. 2

LS mean change from baseline in trough FEV₁ vs. placebo at week 24 in ICS users a and non-ICS users b (pooled ITT population) **P < 0.01 vs. placebo; ***P < 0.001 vs. placebo; ^†† P < 0.01 vs. aclidinium 400 μg; ^‡‡‡ P < 0.001 vs. formoterol 12 μg; ^§ P < 0.05 vs. aclidinium/formoterol 400/6 μg. Analyses based on the mixed model for repeated measures: treatment effects and treatment comparisons. Error bars represent 95% confidence intervals. Patient numbers for the placebo groups were: for patients using ICS, n = 137, for patients not using ICS, n = 254. FEV ₁ forced expiratory volume in 1 s, ICS inhaled corticosteroid, ITT intent-to-treat, LS least squares, mL millilitre