title: The effect of aclidinium bromide on daily respiratory symptoms of COPD, measured using the Evaluating Respiratory Symptoms in COPD (E-RS: COPD) diary: pooled analysis of two 6-month Phase III studies.
abstract: Reducing the severity of respiratory symptoms is a key goal in the treatment of chronic obstructive pulmonary disease (COPD). We evaluated the effect of aclidinium bromide 400 μg twice daily (BID) on respiratory symptoms, assessed using the Evaluating Respiratory Symptoms in COPD (E-RS(™): COPD) scale (formerly EXACT-RS).
  
  
  
  Data were pooled from the aclidinium 400 μg BID and placebo arms of two 24-week, double-blind, randomized Phase III studies evaluating aclidinium monotherapy (ATTAIN) or combination therapy (AUGMENT COPD I) in patients with moderate to severe airflow obstruction. Patients were stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) Groups A-D. Change from baseline in E-RS scores, proportion of responders (patients achieving pre-defined improvements in E-RS scores), and net benefit (patients who improved minus patients who worsened) were analyzed.
  
  
  
  Of 1210 patients, 1167 had data available for GOLD classification. Mean (standard deviation) age was 63.2 (8.6) years, 60.7 % were male, and mean post-bronchodilator forced expiratory volume in 1 s was 54.4 % predicted. Compared with placebo, aclidinium 400 μg BID significantly improved RS-Total (2.38 units vs 0.79 units, p < 0.001) and domain scores (all p < 0.001) at Week 24, and doubled the likelihood of being an RS-Total score responder (p < 0.05), irrespective of GOLD group. The net benefit for RS-Total (Overall: 56.9 % vs 19.4 %; A + C: 65.7 % vs 6.3 %; B + D: 56.0 % vs 20.8 %, for aclidinium 400 μg BID and placebo respectively; all p < 0.05) and domain scores (all p < 0.05) was significantly greater with aclidinium compared with placebo, in both GOLD Groups A + C and B + D.
  
  
  
  Aclidinium 400 μg BID significantly improved respiratory symptoms regardless of the patients' level of symptoms at baseline. Net treatment benefit was similar in patients with low or high levels of symptoms.
  
  
  
  ATTAIN (ClinicalTrials.gov identifier: NCT01001494 ) and AUGMENT COPD I (ClinicalTrials.gov identifier: NCT01437397 ).
authors.affiliation: St George's, University of London, London, UK. pjones@sgul.ac.uk.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Jones
authors.affiliation: Evidera, Bethesda, MD, USA.
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Leidy
authors.affiliation: Evidera, Bethesda, MD, USA.
authors.forename: Asha
authors.initials: A
authors.lastname: Hareendran
authors.affiliation: AstraZeneca PLC, Barcelona, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Lamarca
authors.affiliation: AstraZeneca PLC, Barcelona, Spain.
authors.forename: Ferran
authors.initials: F
authors.lastname: Chuecos
authors.affiliation: AstraZeneca PLC, Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Garcia Gil
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D017326:Clinical Trials, Phase III as Topic; D018450:Disease Progression; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; 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; D012119:Respiration / Q000187:drug effects*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014326:Tropanes / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists; D014326:Tropanes; C542859:aclidinium bromide
keywords: Cohort; Exacerbation risk; Morning symptoms; Nighttime symptoms; Prospective; Retrospective