title: Immediate salbutamol responsiveness does not predict long-term benefits of indacaterol in patients with chronic obstructive pulmonary disease.
abstract: The purpose of this study was to evaluate the correlation between immediate responsiveness with the short-acting β2-agonist salbutamol and effects of treatment with the ultra-long-acting β2-agonist indacaterol in patients with chronic obstructive pulmonary disease (COPD).
  
  
  
  The REVERBREZ study was a phase IV, multicentre, open-label study in which patients with moderate-to-severe COPD received indacaterol 150 μg once-daily for 5 months. The primary endpoint was the correlation between immediate response of forced expiratory volume in 1 s (FEV1) post-inhalation of salbutamol (400 μg) at study entry and the change from baseline in trough FEV1after 1 month of indacaterol. Secondary endpoints included dyspnoea measured by the modified Medical Research Council (mMRC) grade and health-related quality of life measured by the clinical COPD questionnaire (CCQ).
  
  
  
  Of the 602 patients enrolled from 177 centres in France, 543 patients received at least one indacaterol dose, 512 patients completed 1 month of indacaterol treatment (primary endpoint), and 400 patients completed 5 months of treatment. At study entry, mean FEV1values before and after salbutamol inhalation were 1.54 ± 0.50 L and 1.65 ± 0.53 L, respectively. Based on the magnitude of an immediate response of FEV1after salbutamol inhalation at study entry, patients were classified into reversible (Rv, ≥12% and ≥200 mL from pre-salbutamol value; n = 106) and non-reversible (NRv, <12% or <200 mL from pre-salbutamol value; n = 431) groups. After 1 month of indacaterol treatment, mean absolute and relative difference in trough FEV1were 100 mL and 9%, respectively. No significant correlation was found between the immediate FEV1response to salbutamol at study entry and change from baseline in trough FEV1after 1 month of indacaterol treatment (correlation coefficient = 0.056 [95% CI;-0.032, 0.144] for absolute response and 0.028 [95% CI;-0.06, 0.116] for relative response). At all subsequent visits, mMRC and CCQ scores, and FEV1improved from baseline with no significant difference between the Rv and NRv groups.
  
  
  
  Immediate FEV1response to salbutamol did not predict the long-term benefits observed with indacaterol treatment in patients with COPD. Patients considered reversible or non-reversible to salbutamol showed comparable improvements in lung function, dyspnoea and health-related quality of life.
  
  
  
  ClinicalTrials.gov: NCT01272362 . Date: January 5, 2011.
authors.affiliation: Respiratory Medicine, APHP-Hôpital Cochin-Université Paris Descartes, 27 rue du Faubourg St Jacques, Sorbonne Paris Cité, Paris, 75014, France. pierre-regis.burgel@aphp.fr.
authors.forename: Pierre-Régis
authors.identifier: 0000-0003-0903-9828
authors.initials: PR
authors.lastname: Burgel
authors.affiliation: Respiratory Medical Department, Novartis Pharma SAS, Rueil-Malmaison, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Le Gros
authors.affiliation: Respiratory Medical Department, Novartis Pharma SAS, Rueil-Malmaison, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Decuypère
authors.affiliation: Respiratory Medical Department, Novartis Pharma SAS, Rueil-Malmaison, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bourdeix
authors.affiliation: Pulmonary Department, CHU de Lille, Université de Lille, Lille, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Perez
authors.affiliation: Respiratory Medicine, INSERM UMRS 903, Hôpital Maison Blanche-CHU de Reims, Reims, France.
authors.forename: Gaëtan
authors.initials: G
authors.lastname: Deslée
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage*; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004417:Dyspnea / Q000188:drug therapy; D005260:Female; D005541:Forced Expiratory Volume; D005602:France; D006801:Humans; D007189:Indans / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D011788:Quality of Life; D015363:Quinolones / Q000008:administration & dosage*; D014797:Vital Capacity
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D007189:Indans; D015363:Quinolones; C510790:indacaterol; D000420:Albuterol
keywords: COPD; Indacaterol; Reversibility; Salbutamol