To assess the impact of budesonide/formoterol (BUD/FORM) added to tiotropium (TIO) on lung function, morning symptoms, morning activities (getting washed, dried, dressed, eating breakfast, walking at home), reliever use and speed of onset of effect, in COPD patients.
660 COPD patients ≥40 years, pre-bronchodilator FEV1 ≤50% predicted normal and FEV1/VC <70%, eligible for ICS/LABA combination therapy were randomized in a 12-week double-blind, parallel-group, multicenter study (NCT00496470), to receive TIO 18μg qd + BUD/FORM 320/9μg bid or TIO 18μg qd + placebo bid.
BUD/FORM+TIO increased pre-dose FEV1 by 6% (65ml; ratio 1.06, p<0.001) and post-dose FEV1 by 11% (123ml and 131ml at 5 and 60 minutes, respectively; ratio 1.11, both p<0.001) versus TIO alone. The onset of effect of BUD/FORM+TIO was significantly more rapid throughout the study than with TIO alone (clinic FEV1 5 minutes post-dose: week 1 and 12, both p<0.001). BUD/FORM+TIO improved morning FEV1 at home (bedside) versus TIO alone (baseline to last week of treatment, 128ml, 185ml and 186ml pre-, 5- and 15 minutes post-dose, respectively, all p<0.001). Morning symptoms improved pre-dose (mean difference –0.12 [95% CI –0.17, –0.06], p<0.001) and 5 and 15 minutes post-dose (mean difference –0.15 [95% CI –0.22, –0.08] and –0.13 [95% CI –0.20, –0.06], respectively, both p<0.001) with BUD/FORM+TIO versus TIO alone. More BUD/FORM+TIO patients showed ≥4 unit improvements (MCID) in the St. George's Respiratory Questionnaire for COPD (SGRQ-C) than patients receiving TIO alone (50% versus 40%, p=0.016). Changes in total morning activity score were apparent at week 1, favoring BUD/FORM+TIO (mean difference 0.07 [95% CI 0.01, 0.14], p=0.027), further improving at week 12 (0.18 [95% CI 0.09, 0.27], p<0.001). BUD/FORM+TIO reduced daytime reliever use versus TIO alone (–0.51 inhalations, p<0.001); approximately 80% of this reduction was due to reduction in morning reliever use (mean: –0.40 inhalations, p<0.001).
BUD/FORM+TIO causes rapid and greater improvements in lung function, morning activities and symptoms, with reduced morning reliever use, than TIO alone.
BUD/FORM added to TIO is of benefit in the management of COPD.
Tobias Welte, Grant monies (from industry related sources) The Department of Respiratory Medicine, Hannover Medical School, Germany, has received funding for basic research from AstraZeneca.; Shareholder GE, SP and TP hold shares in AstraZeneca.; Employee GE, SP and TP are full time employees of AstraZeneca.; Consultant fee, speaker bureau, advisory committee, etc. TW has received honoraria for lectures from AstraZeneca and is a member of the national and international advisory boards for AstraZeneca. PH has participated on medical advisory boards for the following companies: Abbott, Actelion, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Nycomed, Pfizer and conducted continuing health education activities for the following companies: Actelion, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Pfizer and has conducted industry-sponsored clinical research trials for the following companies: Actelion, AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Novartis, Nycomed, Paringenix, Pfizer, ZLB Behring. MM has received honoraria for lecturing from AstraZeneca, Bayer Schering, Boehringer Ingelheim and Pfizer and has received honoraria for consultancy from AstraZeneca, Bayer Schering, Boehringer Ingelheim, Pfizer, GlaxoSmithKline and Nycomed.; No Product/Research Disclosure Information