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

Pierre-Régis Burgel, Vincent Le Gros, Laurent Decuypère, Isabelle Bourdeix, Thierry Perez, Gaëtan Deslée, Pierre-Régis Burgel, Vincent Le Gros, Laurent Decuypère, Isabelle Bourdeix, Thierry Perez, Gaëtan Deslée

Abstract

Background: 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).

Methods: 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 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.

Trial registration: ClinicalTrials.gov: NCT01272362 . Date: January 5, 2011.

Keywords: COPD; Indacaterol; Reversibility; Salbutamol.

Figures

Fig. 1
Fig. 1
Study flow chart. Data presented are n (%); *During the washout period, patients received salbutamol as a rescue medication; ** All patients received indacaterol
Fig. 2
Fig. 2
Correlation between ∆ trough FEV1 at 1 month (Visit 3-Visit 2) with indacaterol therapy and a absolute FEV1 reversibility and b relative FEV1 reversibility to salbutamol at Visit 1. CI, confidence interval; FEV1, forced expiratory volume in 1 s; V1, Visit 1; V2, Visit 2; V3, Visit 3
Fig. 3
Fig. 3
a Mean change in trough FEV1 (ml) from baseline and b proportion of patients reaching MCID for FEV1 during treatment with indacaterol in reversible (Rv) and non-reversible (NRv) groups. FEV1, forced expiratory volume in 1 s; MCID, minimal clinically important difference; NRv, non-reversible groups; Rv, reversible groups
Fig. 4
Fig. 4
Proportion of patients achieving (a) ≥1 point improvement in mMRC score and b ≥0.4 point improvement in CCQ scores during treatment with indacaterol. CCQ, clinical COPD questionnaire; mMRC, modified Medical Research Council; NRv, non-reversible groups; Rv, reversible groups

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