Introduction and objectives This was a secondary analysis, stratified by concomitant inhaled corticosteroid (ICS) use, based on pooled data from ACLIFORM (NCT01462942) and AUGMENT (NCT01437397), two Phase III, 24-week, randomised, double-blind studies of twice-daily aclidinium/formoterol (AB/FF) fixed-dose combination in patients with moderate to severe airflow obstruction.
Methods Patients received twice-daily AB/FF 400/12 μg, AB/FF 400/6 μg, AB 400 μg, FF 12 μg or placebo (PBO). Any baseline ICS use was continued throughout. Assessments: change from baseline in 1-hour morning post-dose and morning pre-dose (trough) forced expiratory volume in 1 s (FEV1) at Week 24 and Transition Dyspnoea Index (TDI) score (pre-planned), rate of exacerbations and adverse events (AEs).
Results Analyses included 3398 patients (mean age 63.5 years; 60.5% male; baseline ICS use range 38.7–40.0%). In patients using ICS, AB/FF 400/12 µg improved post-dose FEV1, trough FEV1 (Table 1), and TDI vs PBO by 297 mL, 145 mL and 1.59 units, respectively (all p < 0.001). In addition, in patients receiving concomitant ICS, AB/FF 400/12 µg improved post-dose FEV1 and trough FEV1 (Table 1) by 109 mL and 71 mL, respectively, vs FF alone (both p < 0.001) and by 151 mL and 54 mL, respectively, vs AB alone (p < 0.001 and p < 0.05, respectively). In patients not using ICS, there were improvements with AB/FF 400/12 µg in post-dose FEV1, trough FEV1 (Table 1) and TDI of 290 mL, 135 mL and 1.36 units vs PBO, respectively (all p < 0.001). The exacerbation rate was higher in patients using ICS (0.67) vs those who did not (0.36) and AB/FF 400/12 µg significantly reduced the rate of exacerbations vs PBO (p < 0.05; Table 1). The overall AE frequency was similar throughout (range with ICS, 54.8–60.7%; without, 56.0–60.3%). The most common AEs across patient groups were COPD exacerbation, nasopharyngitis and headache, irrespective of ICS use.
Conclusion In this analysis, aclidinium/formoterol 400/12 µg twice daily improved bronchodilation and dyspnoea in patients independent of ICS use and reduced exacerbations in patients using ICS. Combining AB and FF along with an ICS increased bronchodilation vs either monotherapy. AE frequencies were similar between the patient groups, regardless of ICS use.