The efficacy of aclidinium/formoterol on lung function and symptoms in patients with COPD categorized by symptom status: a pooled analysis

Abstract

Background

Patients with chronic obstructive pulmonary disease (COPD) experience respiratory symptoms, which impair quality of life. This pooled analysis of two Phase III studies assessed the impact of aclidinium/formoterol on patients with COPD categorized by symptom status.

Methods

Data were pooled from two 24-week, randomized, placebo-controlled studies of twice-daily aclidinium/formoterol 400/12 µg in moderate-to-severe COPD (ACLIFORM [NCT1462942] and AUGMENT [NCT1437397]). These post hoc analyses evaluated the efficacy of aclidinium/formoterol versus placebo or monotherapies in patients defined as less/more symptomatic by a) Evaluating Respiratory Symptoms (E-RS™) score ≥10/<10 and b) Baseline Dyspnea Index score <7/≥7. Endpoints included trough and 1-hour morning postdose forced expiratory volume in 1 second (FEV₁), Transition Dyspnea Index, E-RS total score, early-morning and nighttime symptom severity, early-morning limitation of activities, and exacerbation rate.

Results

Data for 3,394 patients were analyzed (mean age: 63.5 years; 60.5% male). In both definitions of less and more symptomatic patients, aclidinium/formoterol improved 1-hour morning postdose FEV₁ from baseline at week 24 versus placebo (P<0.001) and both monotherapies (P<0.05). Aclidinium/formoterol improved trough FEV₁ from baseline in both groups versus placebo (P<0.05) and formoterol (P<0.05); improvements were greater in more symptomatic patients. Improvements versus aclidinium were also observed in more symptomatic patients (P<0.05). Aclidinium/formoterol improved dyspnea, early-morning symptom severity, and limitation of activities versus placebo in both less and more symptomatic patients (P<0.001). In more symptomatic patients, aclidinium/formoterol also improved E-RS total score and severity of nighttime symptoms from baseline versus placebo and one or both monotherapies (P<0.05). The rate of moderate/severe exacerbations was reduced with aclidinium/formoterol versus placebo in more symptomatic patients.

Conclusion

Aclidinium/formoterol 400/12 µg provided consistent improvements in bronchodilation and symptoms versus monotherapies and reduced exacerbations versus placebo in more symptomatic patients with moderate-to-severe COPD, regardless of the definition used. Furthermore, patients with a low symptom burden achieved benefits with aclidinium/formoterol versus monotherapies in postdose FEV₁, dyspnea, and early-morning symptoms.

Keywords:

• aclidinium
• formoterol
• COPD
• lung function
• dyspnea
• symptoms

Acknowledgments

The authors would like to thank all of the patients and their families, the team of investigators, research nurses, and operations staff involved in these studies. This study was funded by Almirall SA, Barcelona, Spain. The authors would also like to thank Jennifer Higginson, PhD, of Complete Medical Communications, who provided medical writing support under the direction of the authors, funded by AstraZeneca.

Disclosure

MM has received compensation for speaking/consultancy from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Esteve, Gebro Pharma, GlaxoSmithKline, MedImmune, Menarini, Nycomed, Novartis, Pfizer, Talecris-Grifols, and Takeda. KRC has received grants from Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, CSL Behring, Forest Laboratories, Genentech, GlaxoSmithKline, Grifols, Novartis, and Roche.

In the past 3 years, KRC has received compensation for consulting with AstraZeneca, Baxter, Boehringer Ingelheim, CSL Behring, GlaxoSmithKline, Grifols, Kamada, Novartis, Nycomed, Roche, and Telacris; has undertaken research funded by Amgen, AstraZeneca, Baxter, Boehringer Ingelheim, CSL Behring, Forest Labs, GlaxoSmithKline, Grifols, Novartis, Roche, and Takeda; and has participated in continuing medical education activities sponsored in whole or in part by AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Grifols, Merck Frosst, Novartis, Pfizer, and Takeda. He is participating in research funded by the Canadian Institutes of Health Research operating grant entitled: Canadian Cohort Obstructive Lung Disease (CanCOLD). KRC holds the GSK-CIHR Research Chair in Respiratory Health Care Delivery at the University Health Network, Toronto, Canada.

FC, AR, and EGG are employees of AstraZeneca.

The authors report no other conflicts of interest in this work.