The efficacy of aclidinium/formoterol on lung function and symptoms in patients with COPD categorized by symptom status: a pooled analysis.
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 [NCT01462942] and AUGMENT [NCT01437397]). 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.


CONCLUSIONS
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.
Department of Pneumology, Vall d'Hebron University Hospital, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.
Marc
M
Miravitlles
Asthma & Airway Centre, University Health Network, Toronto Western Hospital and University of Toronto, Toronto, ON, Canada.
Kenneth R
KR
Chapman
Global Medicines Development, AstraZeneca PLC, Barcelona, Spain.
Ferran
F
Chuecos
Global Medical Affairs, AstraZeneca PLC, Barcelona, Spain.
Anna
A
Ribera
Global Medicines Development, AstraZeneca PLC, Barcelona, Spain.
Esther Garcia
EG
Gil
D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002940:Circadian Rhythm; D017326:Clinical Trials, Phase III as Topic; D004338:Drug Combinations; D017079:Exercise Tolerance; D005260:Female; D005541:Forced Expiratory Volume; D000068759:Formoterol Fumarate / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D020127:Recovery of Function; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014326:Tropanes / Q000008:administration & dosage* / Q000009:adverse effects
D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D004338:Drug Combinations; D018727:Muscarinic Antagonists; D014326:Tropanes; C542859:aclidinium bromide; D000068759:Formoterol Fumarate
COPD; aclidinium; dyspnea; formoterol; lung function; symptoms