Immediate salbutamol responsiveness does not predict long-term benefits of indacaterol in patients with chronic obstructive pulmonary disease

Background: The purpose of this study was to evaluate the correlation between immediate responsiveness with the short-acting beta(2)-agonist salbutamol and effects of treatment with the ultra-long-acting beta(2)-agonist indacaterol in patients with chronic obstructive pulmonary disease (COPD). Methods: The REVERBREZ study was a phase IV, multicentre, open-label study in which patients with moderate-to-severe COPD received indacaterol 150 mu g 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 mu g) at study entry and the change from baseline in trough FEV1 after 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). Results: 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 FEV1 values 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 FEV1 after 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 FEV1 were 100 mL and 9%, respectively. No significant correlation was found between the immediate FEV1 response to salbutamol at study entry and change from baseline in trough FEV1 after 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 FEV1 improved from baseline with no significant difference between the Rv and NRv groups. Conclusions: Immediate FEV1 response 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.