Donald Tashkin1, Steven Kesten. 1. Pulmonary Division, David Geffen School of Medicine at the University of California at Los Angeles, 90095, USA. DTashkin@mednet.ucla.edu
Abstract
OBJECTIVES: To determine whether long-term symptomatic improvement occurs in COPD patients with maintenance bronchodilator therapy despite a nonsignificant short-term improvement in FEV(1) following bronchodilator inhalation obtained at a single time point. METHODS: Data obtained during two identical 1-year, placebo-controlled trials of tiotropium, 18 micro g once daily, were analyzed retrospectively to determine the associations of long-term improvements in lung function and patient health status with short-term improvements in FEV(1), as measured on the first day of treatment. Based on the presence or absence of a short-term improvement in FEV(1) of > or = 12% and > or = 200 mL, respectively, patients who had been treated with tiotropium were characterized as being responsive to tiotropium (TIO-R) or poorly responsive to tiotropium (TIO-PR). RESULTS: Baseline characteristics were similar other than baseline FEV(1), which was higher in the TIO-R group than in both the TIO-PR and placebo groups (p < 0.05). Baseline FEV(1) was 1.08 L in the TIO-R group (n = 263), 0.95 L in the TIO-PR (n = 255), and 0.99 L in the placebo group (n = 328). The mean (+/- SD) morning predose FEV(1) at 1 year significantly (p < 0.001) improved in patients in both of the tiotropium treatment subgroups (TIO-R group, 212 +/- 17 mL; TIO-PR group, 94 +/- 17 mL) relative to those treated with placebo. Statistically significant improvements in both tiotropium-treated groups also were noted over 1 year for dyspnea (p < 0.001), as assessed by the transition dyspnea index (TDI) [TIO-R group, 1.36 +/- 0.23 L; TIO-PR group, 0.86 +/- 0.23 L] relative to the placebo group. Patient health status assessed by the St. George Respiratory Questionnaire (SGRQ) showed statistically significant improvements over placebo for the TIO-R and TIO-PR groups (-3.96 +/- 0.99 and -3.05 +/- 1.00 L, respectively; p < 0.005). There was a significant correlation of the first-dose short-term FEV(1) response to the end-of-trial trough response (r = 0.43), but there was only a weak correlation to TDI focal score (r = 0.17) or SGRQ total score (r= -0.12). CONCLUSIONS:Tiotropium was effective in the treatment of patients with COPD, irrespective of the presence or absence of a short-term response on the first day of treatment. The short-term bronchodilator response should not be used as a definitive criterion for prescribing long-term treatment with inhaled bronchodilators.
RCT Entities:
OBJECTIVES: To determine whether long-term symptomatic improvement occurs in COPDpatients with maintenance bronchodilator therapy despite a nonsignificant short-term improvement in FEV(1) following bronchodilator inhalation obtained at a single time point. METHODS: Data obtained during two identical 1-year, placebo-controlled trials of tiotropium, 18 micro g once daily, were analyzed retrospectively to determine the associations of long-term improvements in lung function and patient health status with short-term improvements in FEV(1), as measured on the first day of treatment. Based on the presence or absence of a short-term improvement in FEV(1) of > or = 12% and > or = 200 mL, respectively, patients who had been treated with tiotropium were characterized as being responsive to tiotropium (TIO-R) or poorly responsive to tiotropium (TIO-PR). RESULTS: Baseline characteristics were similar other than baseline FEV(1), which was higher in the TIO-R group than in both the TIO-PR and placebo groups (p < 0.05). Baseline FEV(1) was 1.08 L in the TIO-R group (n = 263), 0.95 L in the TIO-PR (n = 255), and 0.99 L in the placebo group (n = 328). The mean (+/- SD) morning predose FEV(1) at 1 year significantly (p < 0.001) improved in patients in both of the tiotropium treatment subgroups (TIO-R group, 212 +/- 17 mL; TIO-PR group, 94 +/- 17 mL) relative to those treated with placebo. Statistically significant improvements in both tiotropium-treated groups also were noted over 1 year for dyspnea (p < 0.001), as assessed by the transition dyspnea index (TDI) [TIO-R group, 1.36 +/- 0.23 L; TIO-PR group, 0.86 +/- 0.23 L] relative to the placebo group. Patient health status assessed by the St. George Respiratory Questionnaire (SGRQ) showed statistically significant improvements over placebo for the TIO-R and TIO-PR groups (-3.96 +/- 0.99 and -3.05 +/- 1.00 L, respectively; p < 0.005). There was a significant correlation of the first-dose short-term FEV(1) response to the end-of-trial trough response (r = 0.43), but there was only a weak correlation to TDI focal score (r = 0.17) or SGRQ total score (r= -0.12). CONCLUSIONS:Tiotropium was effective in the treatment of patients with COPD, irrespective of the presence or absence of a short-term response on the first day of treatment. The short-term bronchodilator response should not be used as a definitive criterion for prescribing long-term treatment with inhaled bronchodilators.
Authors: Dheeraj Gupta; Ritesh Agarwal; Ashutosh Nath Aggarwal; V N Maturu; Sahajal Dhooria; K T Prasad; Inderpaul S Sehgal; Lakshmikant B Yenge; Aditya Jindal; Navneet Singh; A G Ghoshal; G C Khilnani; J K Samaria; S N Gaur; D Behera Journal: Lung India Date: 2013-07