Efficacy and safety of aclidinium/formoterol fixed-dose combination in patients with COPD, stratified by ICS use

Background: A secondary analysis of pooled data, stratified by concomitant inhaled corticosteroid (ICS) use, is presented from ACLIFORM (NCT01462942) and AUGMENT (NCT01437397), two Phase III, 24-week, randomised, double-blind studies of twice-daily (BID) aclidinium/formoterol (AB/FF) fixed-dose combination in patients (pts) with moderate to severe airflow obstruction.

Methods: Pts received BID AB/FF 400/12 µg, AB/FF 400/6 µg, AB 400 µg, FF 12 µg or placebo (PB). Assessments: change from baseline in 1-hour morning post-dose and morning pre-dose (trough) forced expiratory volume in 1 second (FEV₁) at Week 24, Transition Dyspnoea Index (TDI) score (pre-planned), exacerbation rate and adverse events (AEs).

Results: Analyses included 3398 pts (mean age 63.5 years; 60.5% male; baseline ICS use range 38.7 – 40.0%). AB/FF 400/12 µg with ICS improved post-dose FEV₁, trough FEV₁ (Table), and TDI vs. PB by 297 mL, 145 mL and 1.59 units, respectively (all p < 0.001). In addition, AB/FF 400/12 µg with ICS improved post-dose FEV₁ and trough FEV₁ (Table) 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). AB/FF 400/12 µg without ICS improved post-dose FEV₁, trough FEV₁ (Table) and TDI by 290 mL, 135 mL and 1.36 units vs. PB, respectively (all p < 0.001). Exacerbation rates were higher with ICS (0.67) vs. without (0.36); AB/FF 400/12 µg significantly reduced exacerbations vs. PB in ICS users (p < 0.05; Table). AE frequency was similar throughout (range with ICS, 54.8 – 60.7%; without, 56.0 – 60.3%). Most common AEs across pt groups were COPD exacerbation, nasopharyngitis and headache, regardless of ICS use.

Conclusion: AB/FF 400/12 µg BID improved bronchodilation and dyspnoea regardless of ICS use and reduced exacerbations in pts using ICS. AE frequency was similar across pt groups, regardless of ICS use.

Tab. 1: Change from baseline in morning pre-dose (trough) FEV₁ at Week 24 and rate of exacerbations by concomitant ICS use

	AB/FF 400/12 µg BID	AB/FF 400/6 µg BID	AB 400 µg BID	FF 12 µg BID	Placebo BID
LS mean change from baseline in morning pre-dose (trough) FEV1 at Week 24 by ICS use, mL*
ICS use	98***	47***	44***	27**	-47
No ICS use	85***	71***	71***	18***	-50
Rate of exacerbations per patient/year by ICS use b
ICS use	0.40*	0.53	0.59	0.45	0.67
No ICS use	0.31	0.27	0.29	0.44	0.36
aAnalysis based on the mixed model for repeated measures: treatment effects and treatment comparisons bAnalysis based on the log-linear model *p < 0.05 vs. placebo; **p < 0.01 vs. placebo; ***p < 0.0001 vs. placebo AB, aclidinium bromide; BID, twice daily; FEV1, forced expiratory volume in 1 second; FF, formoterol fumarate; ICS, inhaled corticosteroid; LS, least squares

Funding

This study was funded by Almirail S.A., Barcelona, Spain, and Forest Laboratories LLC, a subsidiary of Actavis PLC, New York, USA. Medical writing support, funded by AstraZeneca PLC, Barcelona, Spain, was provided by Richard Knight of Complete Medical Communications.