title: Characterisation and impact of reported and unreported exacerbations: results from ATTAIN.
abstract: The frequency and impact of exacerbations identified using healthcare resource utilisation (HCRU) or the EXAcerbations of Chronic pulmonary disease Tool (EXACT) were compared prospectively in a 24-week, phase III trial (ATTAIN). Patients with moderate-to-severe chronic obstructive pulmonary disease received twice-daily aclidinium 200 μg, aclidinium 400 μg or placebo. All HCRU events were reported to physicians. "EXACT-identified" events were categorised as "EXACT-reported" (detected by EXACT and reported to the physician) and "EXACT-unreported" (detected but not reported). Health status was measured using the St George's Respiratory Questionnaire (SGRQ). Annualised EXACT-identified event rates were higher in all study arms (placebo 1.39, aclidinium 200 μg 1.00 and aclidinium 400 μg 0.98 per patient per year) versus HCRU (placebo 0.60, aclidinium 200 μg 0.43 and aclidinium 400 μg 0.40 per patient per year). Concordance between methods was low (kappa 0.16). Aclidinium reduced EXACT-identified events (rate ratio versus placebo: aclidinium 200 μg 0.72 and aclidinium 400 μg 0.71; both p<0.05); HCRU events were similarly reduced. At week 24, SGRQ scores improved (-6.6 versus baseline) in patients with no event during weeks 1-12; improvements were significantly smaller in patients with HCRU events (-3.4; p=0.036) or EXACT-unreported events (-3.0; p=0.002). Unreported events were more frequent than reported events. Both had similar negative impact on health status. Aclidinium reduced the frequency of both types of event.
authors.affiliation: Division of Clinical Science, St George's, University of London, London, UK pjones@sgul.ac.uk.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Jones
authors.affiliation: R&D Centre, Almirall, Barcelona, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Lamarca
authors.affiliation: R&D Centre, Almirall, Barcelona, Spain.
authors.forename: Ferran
authors.initials: F
authors.lastname: Chuecos
authors.affiliation: Medicines Evaluation Unit, University Hospital of South Manchester, Manchester, UK.
authors.forename: Dave
authors.initials: D
authors.lastname: Singh
authors.affiliation: Thorax Institute, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain FISIB, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Mallorca, Spain.
authors.forename: Alvar
authors.initials: A
authors.lastname: Agustí
authors.affiliation: Dept of Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Bateman
authors.affiliation: R&D Centre, Almirall, Barcelona, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: de Miquel
authors.affiliation: Forest Research Institute, Forest Laboratories Inc., Jersey City, NJ, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Caracta
authors.affiliation: R&D Centre, Almirall, Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Garcia Gil
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology* / Q000628:therapy*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014326:Tropanes / Q000008:administration & dosage*
chemical_list: D000305:Adrenal Cortex Hormones; D001993:Bronchodilator Agents; D014326:Tropanes; C542859:aclidinium bromide